The laboratory rat has been used for a long time as the model of choice in several biomedical disciplines. Numerous inbred strains have been isolated, displaying a wide range of phenotypes and providing many models of human traits and diseases. Rat genome mapping and genomics was considerably developed in the last decades. The availability of these resources has stimulated numerous studies aimed at discovering causal disease genes by positional identification. Numerous rat genes have now been identified that underlie monogenic or complex diseases and remarkably, these results have been translated to the human in a significant proportion of cases, leading to the identification of novel human disease susceptibility genes, helping in studying the mechanisms underlying the pathological abnormalities and also suggesting new therapeutic approaches. In addition, reverse genetic tools have been developed. Several genome-editing methods were introduced to generate targeted mutations in genes the function of which could be clarified in this manner [generally these are knockout mutations]. Furthermore, even when the human gene causing a disease had been identified without resorting to a rat model, mutated rat strains (in particular KO strains) were created to analyze the gene function and the disease pathogenesis. Today, over 350 rat genes have been identified as underlying diseases or playing a key role in critical biological processes that are altered in diseases, thereby providing a rich resource of disease models. This article is an update of the progress made in this research and provides the reader with an inventory of these disease genes, a significant number of which have similar effects in rat and humans.
Why map and identify genes for rat disease phenotypes or related traits? As already pointed out, the laboratory rat (Rattus norvegicus) is more than a big mouse. The mouse is a species which has been the mammalian genetic model of choice for a long time, with an initial focus on monogenic traits. Rat models of monogenic traits and diseases have also been isolated but the rat has essentially been a key model for studies of complex traits in fields such as physiology, cardiovascular and diabetes research, arthritis, pharmacology, toxicology, oncology and neurosciences [1,2,3,4,5,6]. In some situations the rat seems to be a more relevant or faithful model. For instance, the physiology of the rat is extremely well documented, in part because its larger body size affords the opportunity for serial blood draws, which are almost impossible in the mouse; in cardiovascular research , sophisticated surgical manipulations, and physiological measurements such as blood pressure measurements by telemetry are easier to perform and more reliable in rats compared to mice [1, 3]. The rat has also long been a common choice for pharmacology and toxicology studies because it shares a similar pathway with humans for eradicating toxins . With respect to cancer research [9, 10], and more precisely mammary cancer research, it is noteworthy that rat and human carcinomas show similar development and histopathological features [11, 12]; furthermore, rat mammary tumors are strongly hormone dependent for both induction and growth, thus resembling human breast tumors and no virus appears to be involved in rat and human mammary carcinogenesis, unlike mouse mammary carcinogenesis the etiological agent of which is the mouse mammary tumor virus. As stated by Russo “The rat mammary tumor model is well suited for studying in situ and invasive lesions […]. The classification of the tumors matches well with the criteria used in the human pathology, and provides an adequate model for understanding these phases of the human disease” . In addition, there is extensive overlap between human breast and rat mammary cancer susceptibility genomic regions and “the laboratory rat will continue to be an important model organism for researching genetically determined mechanisms of mammary cancer susceptibility that may translate directly to human susceptibility” . In neuroscience research, rats have significant anatomical and behavioral advantages over mice, because they are more sociable and skilled and have complex cognitive abilities; this wider range of social behaviors and a richer acoustic communication system confer the rat advantages in comparison to mouse models to study neuro-developmental disorders and in particular autism [14, 15]. The rat thus provides one with particularly reliable models of human traits or diseases [3, 8, 11,12,13,14,15,16,17] (multiple details emphasizing the value of rat models can be found in these articles).
Numerous rat strains have been created by selective breeding of animals expressing a desired phenotype, generating a very large collection of genetic models of pathological complex, polygenic traits, most of which are quantitative. Interestingly, these strains also provide one with additional phenotypes, which were not selected for. Just as the traits that were selected for, most of these phenotypes are polygenic. All these phenotypes can be used as models of human traits or diseases , implying that the genes underlying these traits or diseases should be identified. Information on rat strains and rat disease models, can be found at the Rat Genome Database (RGD, https://rgd.mcw.edu/) .
In order to give the rat the status of a valuable genetic model, and in particular to identify the genes underlying complex traits by forward genetic approaches and to analyze the relevant biological mechanisms, several tools had to be developed. This has been accomplished. Genetic and chromosome maps have been developed; the genomic sequence of dozens of rat strains has been established; a number of resources have been created to provide investigators with access to genetic, genomic, phenotype and disease-relevant data as well as software tools necessary for their research [3, 20]. Thanks to these resources, positional identification of numerous rat genes underlying monogenic or complex diseases and related traits could be achieved. On the other hand, reverse genetic tools have also been developed. Efficient methods to generate mutant rats became available; sperm N-ethyl-N-nitrosourea (ENU) mutagenesis followed by gene-targeted screening methods lead to the isolation of several mutants, including knockout (KO) strains ( and references therein). Rat ES were successfully derived and could be used for targeted mutations by homologous recombination; more importantly, several methods not relying on the use of ES cells were introduced to generated targeted mutations (often these are KO mutations), namely gene editing by zinc finger nucleases, by transcription activator-like effector nucleases and finally by the clustered regularly interspaced short palindromic repeat (CRISPR/Cas) system . Transgenic rats can also be generated, including humanized rats carrying large chromosomic fragments (“transchromosomic humanized” rats) . Development of these technologies provides the researcher with all the tools required to take advantage of the unique opportunities offered by the rat as leading model for studies different areas of biomedical research [3, 17]. In this review I made an inventory of the rat genes identified as responsible for monogenic or polygenic diseases and related traits. I took into account the rat genes identified by forward genetic methods as well as those inactivated by ENU-mutagenesis and by targeted mutations, the inactivation of which generated a disease or an abnormal phenotype. This update of the progress made in the identification of rat disease genes shows that a considerable number of conserved genes have similar effects on biological traits in rats and humans, establishing the rat as a valuable model in studies of the genetic basis of human diseases and thus providing one with a useful resource of disease models.
Materials and methods
The data (causal genes of rat diseases and related traits) were collected by regular and systematic screening of the biomedical literature, PubMed searches (https://www.ncbi.nlm.nih.gov/) and regular Google Scholar alerts based on the keywords “knockout”, “mutation”, “rat” (spread over several months). In addition, relevant data were retrieved from the RGD (“Disease Portals”), with advices from Jennifer R. Smith. Genes identified by forward genetic means (or by direct molecular sequencing) were considered as suggestive, solid or confirmed, respectively, as indicated in each case in Table 1 (one, two or three asterisks), on the basis of the criterions described in the legend to the table; these criterions are based on the standards discussed by Glazier and coworkers . With respect to the induced mutants, they were included provided they were convincingly shown to be specifically altered. The official gene symbols are used in this article and were obtained from the National Center for Biotechnology Information (https://www.ncbi.nlm.nih.gov/), Gene section. In several instances the original publications did not use the official gene symbol; in these cases, the non-official symbol is indicated in parenthesis in the footnote to the table, where the full name of each gene is described. The position of every gene was also obtained from the NCBI.
The core of this article is a list of the diseases and related traits or phenotypes the causal gene of which was identified in the rat (Table 1). The genes identified by forward genetic methods or, in a few instances, by direct molecular characterization are labeled by asterisks (see legend to table). Also listed are the phenotypes uncovered by reverse genetics methods, either by ENU-mutagenesis followed by selection of the desired mutated gene (these genes are labeled by the symbol ENU), or by targeted gene editing (these genes are labeled by T). Table 1A shows the monogenic traits, and Table 1B the complex traits (in a few cases this distinction is somewhat arbitrary, but in general this is a useful classification). Of note, when a gene was associated with several distinct phenotypes, an entry was created for each phenotype and the gene thus appears several times in the table. When the human homolog gene is known to be causal of the relevant disease or trait, it is also indicated in the table. Furthermore, entries in bold characters indicate that the human gene was found to be causal as a direct translation of the results obtained in the rat.
Identification of rat disease genes by forward genetic methods
The identification of gene(s) underlying a given phenotype typically starts with the mapping of the trait by linkage analysis (backcrosses, intercrosses). In the case of monogenic traits, this approach is generally sufficient to identify the causative gene (positional identification, as illustrated in Table 1A). Identifying genes controlling complex traits is much more difficult [24, 25]; indeed, linkage analyses of such traits lead to the localization of quantitative trait loci (QTLs), which are too large to allow the identification of the causative gene. Complementary strategies are thus required to narrow down the list of candidate genes, such as the generation of congenic lines or/and the use of integrative genomic approaches (as discussed in ). Alternative approaches rely on the use of panels of lines that show a higher level of recombinant events, as a result of crossing parental strains for multiple generations, such as recombinant inbred strains or heterogeneous stocks (as discussed in , for a striking harvest of results derived from the study of a heterogeneous stock, see ). The first complex-trait gene identified is the Cd36 gene, which causes insulin resistance, hyperlipidemia and hypertension in the spontaneously hypertensive rat (SHR) [29, 30]. This identification was based on a combined gene expression micro-array and linkage approach and was definitively proven by in vivo complementation, i.e. transgenic expression of normal Cd36 in the SHR . Last but not least, association was then demonstrated between human CD36 and insulin resistance . Subsequently, the tools of forward genetic studies as well as gene expression and/or computational analysis (integrative genomics) led to the identification of numerous genes underlying rat polygenic traits or diseases, such as blood pressure, cardiac mass, diabetes, inflammation (in particular arthritis, encephalomyelitis), glomerulonephritis, mammary cancer, neurobehavioral traits, proteinuria. In several instances, the results were translated to the human, as illustrated in Table 1 by bold entries. Interestingly, a recently discovered complex trait gene is a long non-coding RNA, itself contained within the 5′ UTR of the Rffl gene (Rffl-lnc1); Rffl-lnc1 shows a 19 bp indel polymorphism which is the precise variation underlying regulation of blood pressure and QT-interval. This work was based on fine and systematic congenic mapping and is the first one to identify quantitative trait nucleotides in a long non-coding RNA . The human homologous region, on chromosome 17, has multiple minor alleles that are associated with shorter QT-intervals and, is some cases, hypertension .
Identifying rat disease genes is not only useful to discover the homologous human disease genes but also helps in studying the mechanisms underlying the pathological abnormalities. After all, this is the essence of an animal model. For instance, the study of the genetic basis of stroke in the stroke-prone SHR strain (SHRSP) led to the conclusion that mitochondrial dysfunction contributes to stroke susceptibility and to hypertensive target organ damage (such as vascular damage); this better understanding of the etiology of the disease can open the door to novel therapies, as briefly discussed below [8, 35, 36].
The importance of rat models in the era of human genetic studies and genome sequencing
The rat is also a useful model to decipher the biological significance of QTLs identified in human genome-wide association studies (GWAS) aimed at understanding the etiology of common human diseases [37, 38]. These studies pint-point human genomic regions controlling a complex trait, and generally contain several genes; the current methods lack the statistical power to pinpoint the human causative gene. Animal model such as the rat provides one with the possibility to knockout or to mutate in more subtle manner each of the rat genes homolog to the human genes contained in a given GWAS locus. In this way, the possible role of each gene can be evaluated. For instance, Flister and co-corkers , studying a multigene GWAS locus controlling blood pressure and renal phenotypes (AGTRAP-PLOD1 locus) used gene targeting in a rat model to test each of the genes contained in this locus. In this way these authors could show that several genes impact hypertension and that multiple causative gene variants cosegregate at this locus; several linked genes thus control blood pressure (Agtrap, Clcn6, Mthfr, Nppa, Plod1). Furthermore, each of the KO rat models so generated can be used to dissect the biological effects of the gene loss of function.
The genetic basis of human diseases is also actively analyzed by whole genome sequencing; such studies have uncovered several genes underlying diseases or related phenotypes [40, 41] and one can thus questioned the importance of genetic analyses in an animal model. As argued and illustrated above, animal models and the rat in particular, remain valuable tools to analyze the biological mechanisms underlying a phenotype. In addition, transgenesis or gene substitution can also be carried out, in which a human allele can be introduced in the relevant KO rat, in order to verify the role of the human mutation. Alternatively, the rat genome can be directly modified to specifically introduce a mutation similar to the one causing the human trait [40, 42]. If the modified rats exhibit defects similar to those observed in the human patients, it can be concluded that the tested human mutation indeed plays a causal role. In addition, similarly to examples mentioned above, such specifically modified rats provide one with models suitable to study the mechanisms responsible for the abnormalities generated by the mutation and also to carry out pharmacological tests and look for possible new therapies .
The need of relevant animal models is also illustrated by the fact that even when the human gene causing a disease is known, mutated rat strains (in particular KO strains) were created to analyze the gene function and the disease pathogenesis (see numerous examples of such gene targetings in Table 1). In 2008, Aitman and coworkers  reported a list of 21 rat disease genes (that had been identified by positional cloning). Here I updated the list of rat disease genes; this inventory added numerous genes identified (or deliberately mutated) after 2008, thereby evaluating progress made in the input of rat disease models. The total rat gene number listed in Table 1 exceeds 350, illustrating the vigor of the rat biomedical research which led to enrichment of numerous disease models, with the translation to humans of disease gene discoveries in rats.
Translation of the rat genetic studies into new treatments of human diseases
The identification of a human disease gene has the potential to develop new therapeutic approaches. For instance, the human gene NCF4 was found to be associated with arthritis as a translation of studies on a rat arthritis model. The gene encodes a component of the NADPH oxidase complex and these studies catalyzed the development of a new therapy for arthritis, based on the use of oxidative-burst inducing substances [43,44,45] (see Table 1B, Arthritis, Ncf1 gene). Another interesting example is that of the gene SHANK3: mutations in this gene lead to a neurodevelopmental disorder known as Phelan-McDermid syndrome; to date, no pharmaceutical compounds targeting core symptoms of this human disease are available. A Shank3-deficient rat model was generated, which showed disabilities similar to those seen in the Phelan-McDermid syndrome and interestingly, the deficits of the mutant rat could be ameliorated by intracerebroventricular oxytocin administration, implying that exogenous oxytocin administration might have therapeutic potential in human patients  (see Table 1A, Phelan-McDermid syndrome model). A third example is provided by the study of rat mutated in the Pde3a gene, which recapitulates the phenotype of HTNB (Hypertension with brachydactyly) human patients: the functional data suggest that soluble guanyly cyclase activation could be suitable for the treatment of HTNB patients  (See Table 1B, Blood pressure section).
This evaluation of progress in the identification of genes causing monogenic or polygenic rat diseases or related phenotypes yielded a list containing over 350 genes. In several instances the result obtained in the rat model was translated to the human, demonstrating that a considerable number of conserved genes have similar effects on biological traits in rats and humans, and thus providing one with a rich and useful resource of disease models (Table 1, bold entries). For instance, the Inppl1 gene was first identified in the rat as a causative gene of type 2 diabetes and this discovery led to the identification of mutations in the homolog gene of diabetic patients [452, 534]. Similarly, a rat paralog of the Fcgr3 gene (Fcgr3-rs) was identified as causing glomerulonephritis, and the result was promptly translated to the human: low copy number of FCGR3B, an orthologue of rat Fcgr3, was associated with glomerulonephritis in the autoimmune disease systemic lupus erythematosus .
Also, as mentioned above, even when the human gene causing a disease had been identified (without resorting to a rat model), mutated rat strains, in particular KO strains, were created to analyze the gene function and the disease pathogenesis, and, potentially, to develop new therapies.
This review illustrates the vigor of the rat biomedical research and its value for understanding the etiology of human diseases and for suggesting new therapies.
Availability of data and materials
Genome wide association study
Nicotinamide adenine dinucleotide phosphate
Quantitative trait locus
Rat Genome Database
Jacob HJ. The rat: a model used in biomedical research. Methods Mol Biol. 2010;597:1–11.
Aitman TJ, Critser JK, Cuppen E, Dominiczak A, Fernandez-Suarez XM, Flint J, et al. Progress and prospects in rat genetics: a community view. Nat Genet. 2008;40(5):516–22.
Aitman T, Dhillon P, Geurts AM. A RATional choice for translational research? Dis Model Mech. 2016;9(10):1069–72.
James MR, Lindpaintner K. Why map the rat? Trends Genet. 1997;13(5):171–3.
Suckow MA, Hankenson FC, Wilson RP, Foley PL. The laboratory rat. 3rd ed: Elsevier; 2020. p. 1180.
Jacob HJ. Functional genomics and rat models. Genome Res. 1999;9(11):1013–6.
Allen PS, Dell’Italia LJ, Esvelt M, Conte ML, Cadillac JM, Myers DD Jr. Cardiovascular research. In: Suckow MA, Hankenson FC, Wilson RP, Foley PL, editors. The laboratory rat. 3rd ed: Elsevier; 2020. p. 927–5.
Hashway SA, Wilding LA. Translational potential of rats in research. In: Suckow MA, Hankenson FC, Wilson RP, Foley PL, editors. The laboratory rat. 3rd ed: Elsevier; 2020. p. 77–88.
Szpirer C. Cancer research in rat models. Methods Mol Biol. 2010;597:445–58.
Nascimento-Gonçalves E, Faustino-Rocha AI, Seixas F, Ginja M, Colaço B, Ferreira R, et al. Modelling human prostate cancer: rat models. Life Sci. 2018;203:210–24.
Russo J. Significance of rat mammary tumors for human risk assessment. Toxicol Pathol. 2015;43(2):145–70.
Russo J, Gusterson BA, Rogers AE, Russo IH, Wellings SR, van Zwieten MJ. Comparative study of human and rat mammary tumorigenesis. Lab Investig. 1990;62(3):244–78.
Sanders J, Samuelson DJ. Significant overlap between human genome-wide association-study nominated breast cancer risk alleles and rat mammary cancer susceptibility loci. Breast Cancer Res. 2014;16(1):R14.
Ellenbroek B, Youn J. Rodent models in neuroscience research: is it a rat race? Dis Model Mech. 2016;9(10):1079–87.
Parker CC, Chen H, Flagel SB, Geurts AM, Richards JB, Robinson TE, et al. Rats are the smart choice: rationale for a renewed focus on rats in behavioral genetics. Neuropharmacology. 2014;76 Pt B:250–8.
Carter CS, Richardson A, Huffman DM, Austad S. Bring back the rat! J Gerontol A Biol Sci Med Sci. 2020;75(3):405–15.
Homberg JR, Wohr M, Alenina N. Comeback of the rat in biomedical research. ACS Chem Neurosci. 2017;8(5):900–3.
Szpirer C, Levan G. Rat gene mapping and genomics. In: Denny P, Kole C, editors. Genome mapping and genomics in laboratory animals. Heidelberg, New York, Dordrecht, London: Springer; 2012. p. 217–56.
Wang SJ, SJF L, Zhao Y, Hayman GT, Smith JR, Tutaj M, et al. Integrated curation and data mining for disease and phenotype models at the Rat Genome Database. Database (Oxford). 2019;2019:baz014.
Shimoyama M, Smith JR, Bryda E, Kuramoto T, Saba L, Dwinell M. Rat genome and model resources. ILAR J. 2017;58(1):42–58.
Mashimo T, Yanagihara K, Tokuda S, Voigt B, Takizawa A, Nakajima R, et al. An ENU-induced mutant archive for gene targeting in rats. Nat Genet. 2008;40(5):514–5.
Meek S, Mashimo T, Burdon T. From engineering to editing the rat genome. Mamm Genome. 2017;28(7–8):302–14.
Kazuki Y, Kobayashi K, Hirabayashi M, Abe S, Kajitani N, Kazuki K, et al. Humanized UGT2 and CYP3A transchromosomic rats for improved prediction of human drug metabolism. Proc Natl Acad Sci U S A. 2019;116(8):3072–81.
Glazier AM, Nadeau JH, Aitman TJ. Finding genes that underlie complex traits. Science. 2002;298(5602):2345–9.
Aitman TJ, Petretto E, Behmoaras J. Genetic mapping and positional cloning. Methods Mol Biol. 2010;597:13–32.
Moreno-Moral A, Petretto E. From integrative genomics to systems genetics in the rat to link genotypes to phenotypes. Dis Model Mech. 2016;9(10):1097–110.
Baud A, Flint J. Identifying genes for neurobehavioural traits in rodents: progress and pitfalls. Dis Model Mech. 2017;10(4):373–83.
Rat Genome Sequencing and Mapping Consortium, Baud A, Hermsen R, Guryev V, Stridh P, et al. Combined sequence-based and genetic mapping analysis of complex traits in outbred rats. Nat Genet. 2013;45(7):767–75.
Pravenec M, Churchill PC, Churchill MC, Viklicky O, Kazdova L, Aitman TJ, et al. Identification of renal Cd36 as a determinant of blood pressure and risk for hypertension. Nat Genet. 2008;40(8):952–4.
Aitman TJ, Glazier AM, Wallace CA, Cooper LD, Norsworthy PJ, Wahid FN, et al. Identification of Cd36 (Fat) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats. Nat Genet. 1999;21(1):76–83.
Pravenec M, Landa V, Zidek V, Musilova A, Kren V, Kazdova L, et al. Transgenic rescue of defective Cd36 ameliorates insulin resistance in spontaneously hypertensive rats. Nat Genet. 2001;27(2):156–8.
Corpeleijn E, van der Kallen CJ, Kruijshoop M, Magagnin MG, de Bruin TW, Feskens EJ, et al. Direct association of a promoter polymorphism in the CD36/FAT fatty acid transporter gene with type 2 diabetes mellitus and insulin resistance. Diabet Med. 2006;23(8):907–11.
Cheng X, Waghulde H, Mell B, Morgan EE, Pruett-Miller SM, Joe B. Positional cloning of quantitative trait nucleotides for blood pressure and cardiac QT-interval by targeted CRISPR/Cas9 editing of a novel long non-coding RNA. PLoS Genet. 2017;13(8):e1006961.
Newton-Cheh C, Eijgelsheim M, Rice KM, de Bakker PI, Yin X, Estrada K, et al. Common variants at ten loci influence QT interval duration in the QTGEN study. Nat Genet. 2009;41(4):399–406.
Rubattu S, Stanzione R, Volpe M. Mitochondrial dysfunction contributes to hypertensive target organ damage: lessons from an animal model of human disease. Oxidative Med Cell Longev. 2016;2016:1067801.
Rubattu S, Di Castro S, Schulz H, Geurts AM, Cotugno M, Bianchi F, et al. Ndufc2 gene inhibition is associated with mitochondrial dysfunction and increased stroke susceptibility in an animal model of complex human disease. J Am Heart Assoc. 2016;5(2):e002701.
Visscher PM, Wray NR, Zhang Q, Sklar P, McCarthy MI, Brown MA, et al. 10 years of GWAS discovery: biology, function, and translation. Am J Hum Genet. 2017;101(1):5–22.
Auer PL, Stitziel NO. Genetic association studies in cardiovascular diseases: do we have enough power? Trends Cardiovasc Med. 2017;27(6):397–404.
Flister MJ, Tsaih SW, O’Meara CC, Endres B, Hoffman MJ, Geurts AM, et al. Identifying multiple causative genes at a single GWAS locus. Genome Res. 2013;23(12):1996–2002.
Peng W, Li M, Li H, Tang K, Zhuang J, Zhang J, et al. Dysfunction of myosin light-chain 4 (MYL4) leads to heritable atrial cardiomyopathy with electrical, contractile, and structural components: evidence from genetically-engineered rats. J Am Heart Assoc. 2017;6(11):e007030.
Smith M. DNA sequence analysis in clinical medicine, proceeding cautiously. Front Mol Biosci. 2017;4:24.
Harony-Nicolas H, Kay M, du Hoffmann J, Klein ME, Bozdagi-Gunal O, Riad M, et al. Oxytocin improves behavioral and electrophysiological deficits in a novel Shank3-deficient rat. Elife. 2017;6:e18904.
Olsson LM, Lindqvist AK, Kallberg H, Padyukov L, Burkhardt H, Alfredsson L, et al. A case-control study of rheumatoid arthritis identifies an associated single nucleotide polymorphism in the NCF4 gene, supporting a role for the NADPH-oxidase complex in autoimmunity. Arthritis Res Ther. 2007;9(5):R98.
Gelderman KA, Hultqvist M, Olsson LM, Bauer K, Pizzolla A, Olofsson P, et al. Rheumatoid arthritis: the role of reactive oxygen species in disease development and therapeutic strategies. Antioxid Redox Signal. 2007;9(10):1541–67.
Hultqvist M, Olofsson P, Gelderman KA, Holmberg J, Holmdahl R. A new arthritis therapy with oxidative burst inducers. PLoS Med. 2006;3(9):e348.
Ercu M, Marko L, Schachterle C, Tsvetkov D, Cui Y, Maghsodi S, et al. Phosphodiesterase 3A and arterial hypertension. Circulation. 2020;142(2):133–49.
Puissant MM, Muere C, Levchenko V, Manis AD, Martino P, Forster HV, et al. Genetic mutation of Kcnj16 identifies Kir5.1-containing channels as key regulators of acute and chronic pH homeostasis. FASEB J. 2019;33(4):5067–75.
St Laurent R, Helm SR, Glenn MJ. Reduced cocaine-seeking behavior in heterozygous BDNF knockout rats. Neurosci Lett. 2013;544:94–9.
King CP, Militello L, Hart A, St Pierre CL, Leung E, Versaggi CL, et al. Cdh13 and AdipoQ gene knockout alter instrumental and Pavlovian drug conditioning. Genes Brain Behav. 2017;16(7):686–98.
Gao JT, Jordan CJ, Bi GH, He Y, Yang HJ, Gardner EL, et al. Deletion of the type 2 metabotropic glutamate receptor increases heroin abuse vulnerability in transgenic rats. Neuropsychopharmacology. 2018;43(13):2615–26.
Yang HJ, Zhang HY, Bi GH, He Y, Gao JT, Xi ZX. Deletion of type 2 metabotropic glutamate receptor decreases sensitivity to cocaine reward in rats. Cell Rep. 2017;20(2):319–32.
Yamamoto T, Izumi-Yamamoto K, Iizuka Y, Shirota M, Nagase M, Fujita T, et al. A novel link between Slc22a18 and fat accumulation revealed by a mutation in the spontaneously hypertensive rat. Biochem Biophys Res Commun. 2013;440(4):521–6.
Dang R, Sasaki N, Nishino T, Nakanishi M, Torigoe D, Agui T. Lymphopenia in Ednrb-deficient rat was strongly modified by genetic background. Biomed Res. 2012;33(4):249–53.
Gariepy CE, Cass DT, Yanagisawa M. Null mutation of endothelin receptor type B gene in spotting lethal rats causes aganglionic megacolon and white coat color. Proc Natl Acad Sci U S A. 1996;93(2):867–72.
Kunieda T, Kumagai T, Tsuji T, Ozaki T, Karaki H, Ikadai H. A mutation in endothelin-B receptor gene causes myenteric aganglionosis and coat color spotting in rats. DNA Res. 1996;3(2):101–5.
Dang R, Torigoe D, Sasaki N, Agui T. QTL analysis identifies a modifier locus of aganglionosis in the rat model of Hirschsprung disease carrying Ednrb(sl) mutations. PLoS One. 2011;6(11):e27902.
Huang J, Dang R, Torigoe D, Li A, Lei C, Sasaki N, et al. Genetic variation in the GDNF promoter affects its expression and modifies the severity of Hirschsprung’s disease (HSCR) in rats carrying Ednrb(sl) mutations. Gene. 2016;575(1):144–8.
Wang J, Dang R, Miyasaka Y, Hattori K, Torigoe D, Okamura T, et al. Null mutation of the endothelin receptor type B gene causes embryonic death in the GK rat. PLoS One. 2019;14(6):e0217132.
Ceccherini I, Zhang AL, Matera I, Yang G, Devoto M, Romeo G, et al. Interstitial deletion of the endothelin-B receptor gene in the spotting lethal (sl) rat. Hum Mol Genet. 1995;4(11):2089–96.
Pridans C, Raper A, Davis GM, Alves J, Sauter KA, Lefevre L, et al. Pleiotropic impacts of macrophage and microglial deficiency on development in rats with targeted mutation of the Csf1r locus. J Immunol. 2018;201(9):2683–99.
Muto T, Miyoshi K, Horiguchi T, Hagita H, Noma T. Novel genetic linkage of rat Sp6 mutation to Amelogenesis imperfecta. Orphanet J Rare Dis. 2012;7:34.
Esumi H, Takahashi Y, Sato S, Nagase S, Sugimura T. A seven-base-pair deletion in an intron of the albumin gene of analbuminemic rats. Proc Natl Acad Sci U S A. 1983;80(1):95–9.
Tsujimura T, Hirota S, Nomura S, Niwa Y, Yamazaki M, Tono T, et al. Characterization of Ws mutant allele of rats: a 12-base deletion in tyrosine kinase domain of c-kit gene. Blood. 1991;78(8):1942–6.
Fleming MD, Romano MA, Su MA, Garrick LM, Garrick MD, Andrews NC. Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport. Proc Natl Acad Sci U S A. 1998;95(3):1148–53.
Berg EL, Pride MC, Petkova SP, Lee RD, Copping NA, Shen Y, et al. Translational outcomes in a full gene deletion of ubiquitin protein ligase E3A rat model of Angelman syndrome. Transl Psychiatry. 2020;10(1):39.
Tokuda S, Kuramoto T, Tanaka K, Kaneko S, Takeuchi IK, Sasa M, et al. The ataxic groggy rat has a missense mutation in the P/Q-type voltage-gated Ca2+ channel alpha1A subunit gene and exhibits absence seizures. Brain Res. 2007;1133(1):168–77.
Quek H, Luff J, Cheung K, Kozlov S, Gatei M, Lee CS, et al. A rat model of ataxia-telangiectasia: evidence for a neurodegenerative phenotype. Hum Mol Genet. 2017;26(1):109–23.
Quek H, Luff J, Cheung K, Kozlov S, Gatei M, Lee CS, et al. Rats with a missense mutation in Atm display neuroinflammation and neurodegeneration subsequent to accumulation of cytosolic DNA following unrepaired DNA damage. J Leukoc Biol. 2017;101(4):927–47.
Scott KE, Schormans AL, Pacoli KY, De Oliveira C, Allman BL, Schmid S. Altered auditory processing, filtering, and reactivity in the Cntnap2 knock-out rat model for neurodevelopmental disorders. J Neurosci. 2018;38(40):8588–604.
Hamilton SM, Green JR, Veeraragavan S, Yuva L, McCoy A, Wu Y, et al. Fmr1 and Nlgn3 knockout rats: novel tools for investigating autism spectrum disorders. Behav Neurosci. 2014;128(2):103–9.
Thomas AM, Schwartz MD, Saxe MD, Kilduff TS. Sleep/wake physiology and quantitative electroencephalogram analysis of the Neuroligin-3 knockout rat model of autism spectrum disorder. Sleep. 2017;40(10):zsx138.
Modi ME, Brooks JM, Guilmette ER, Beyna M, Graf R, Reim D, et al. Hyperactivity and hypermotivation associated with increased striatal mGluR1 signaling in a Shank2 Rat model of autism. Front Mol Neurosci. 2018;11:107.
Kuwamura M, Muraguchi T, Matsui T, Ueno M, Takenaka S, Yamate J, et al. Mutation at the Lmx1a locus provokes aberrant brain development in the rat. Brain Res Dev Brain Res. 2005;155(2):99–106.
Cotroneo MS, Haag JD, Zan Y, Lopez CC, Thuwajit P, Petukhova GV, et al. Characterizing a rat Brca2 knockout model. Oncogene. 2007;26(11):1626–35.
van Boxtel R, Toonen PW, van Roekel HS, Verheul M, Smits BM, Korving J, et al. Lack of DNA mismatch repair protein MSH6 in the rat results in hereditary non-polyposis colorectal cancer-like tumorigenesis. Carcinogenesis. 2008;29(6):1290–7.
Yan HX, Wu HP, Ashton C, Tong C, Ying QL. Rats deficient for p53 are susceptible to spontaneous and carcinogen-induced tumorigenesis. Carcinogenesis. 2012;33(10):2001–5.
van Boxtel R, Kuiper RV, Toonen PW, van Heesch S, Hermsen R, de Bruin A, et al. Homozygous and heterozygous p53 knockout rats develop metastasizing sarcomas with high frequency. Am J Pathol. 2011;179(4):1616–22.
Hansen SA, Hart ML, Busi S, Parker T, Goerndt A, Jones K, et al. Fischer-344 Tp53-knockout rats exhibit a high rate of bone and brain neoplasia with frequent metastasis. Dis Model Mech. 2016;9(10):1139–46.
McCoy A, Besch-Williford CL, Franklin CL, Weinstein EJ, Cui X. Creation and preliminary characterization of a Tp53 knockout rat. Dis Model Mech. 2013;6(1):269–78.
Yoshimi K, Tanaka T, Takizawa A, Kato M, Hirabayashi M, Mashimo T, et al. Enhanced colitis-associated colon carcinogenesis in a novel Apc mutant rat. Cancer Sci. 2009;100(11):2022–7.
Amos-Landgraf JM, Kwong LN, Kendziorski CM, Reichelderfer M, Torrealba J, Weichert J, et al. A target-selected Apc-mutant rat kindred enhances the modeling of familial human colon cancer. Proc Natl Acad Sci U S A. 2007;104(10):4036–41.
Irving AA, Yoshimi K, Hart ML, Parker T, Clipson L, Ford MR, et al. The utility of Apc-mutant rats in modeling human colon cancer. Dis Model Mech. 2014;7(11):1215–25.
Ding L, Shunkwiler LB, Harper NW, Zhao Y, Hinohara K, Huh SJ, et al. Deletion of Cdkn1b in ACI rats leads to increased proliferation and pregnancy-associated changes in the mammary gland due to perturbed systemic endocrine environment. PLoS Genet. 2019;15(3):e1008002.
Pellegata NS, Quintanilla-Martinez L, Siggelkow H, Samson E, Bink K, Hofler H, et al. Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. Proc Natl Acad Sci U S A. 2006;103(42):15558–63.
Okimoto K, Sakurai J, Kobayashi T, Mitani H, Hirayama Y, Nickerson ML, et al. A germ-line insertion in the Birt-Hogg-Dube (BHD) gene gives rise to the Nihon rat model of inherited renal cancer. Proc Natl Acad Sci U S A. 2004;101(7):2023–7.
Yeung RS, Xiao GH, Jin F, Lee WC, Testa JR, Knudson AG. Predisposition to renal carcinoma in the Eker rat is determined by germ-line mutation of the tuberous sclerosis 2 (TSC2) gene. Proc Natl Acad Sci U S A. 1994;91(24):11413–6.
Flister MJ, Hoffman MJ, Lemke A, Prisco SZ, Rudemiller N, O’Meara CC, et al. SH2B3 is a genetic determinant of cardiac inflammation and fibrosis. Circ Cardiovasc Genet. 2015;8(2):294–304.
Luo C, Xie X, Feng X, Lei B, Fang C, Li Y, et al. Deficiency of Interleukin-36 receptor protected cardiomyocytes from ischemia-reperfusion injury in cardiopulmonary bypass. Med Sci Monit. 2020;26:e918933.
Zhou Q, Peng X, Liu X, Chen L, Xiong Q, Shen Y, et al. FAT10 attenuates hypoxia-induced cardiomyocyte apoptosis by stabilizing caveolin-3. J Mol Cell Cardiol. 2018;116:115–24.
Wu TT, Ma YW, Zhang X, Dong W, Gao S, Wang JZ, et al. Myocardial tissue-specific Dnmt1 knockout in rats protects against pathological injury induced by Adriamycin. Lab Invest. 2020;100(7):974–85.
Chen P, Li Z, Nie J, Wang H, Yu B, Wen Z, et al. MYH7B variants cause hypertrophic cardiomyopathy by activating the CaMK-signaling pathway. Sci China Life Sci. 2020; https://doi.org/10.1007/s11427-019-1627-y.
Guo W, Pleitner JM, Saupe KW, Greaser ML. Pathophysiological defects and transcriptional profiling in the RBM20−/− rat model. PLoS One. 2013;8(12):e84281.
Zigler JS Jr, Zhang C, Grebe R, Sehrawat G, Hackler L Jr, Adhya S, et al. Mutation in the betaA3/A1-crystallin gene impairs phagosome degradation in the retinal pigmented epithelium of the rat. J Cell Sci. 2011;124(Pt 4):523–31.
Sinha D, Klise A, Sergeev Y, Hose S, Bhutto IA, Hackler L Jr, et al. betaA3/A1-crystallin in astroglial cells regulates retinal vascular remodeling during development. Mol Cell Neurosci. 2008;37(1):85–95.
Johnson AC, Lee JW, Harmon AC, Morris Z, Wang X, Fratkin J, et al. A mutation in the start codon of gamma-crystallin D leads to nuclear cataracts in the dahl SS/Jr-Ctr strain. Mamm Genome. 2013;24(3–4):95–104.
Yoshida M, Harada Y, Kaidzu S, Ohira A, Masuda J, Nabika T. New genetic model rat for congenital cataracts due to a connexin 46 (Gja3 ) mutation. Pathol Int. 2005;55(11):732–7.
Liska F, Chylikova B, Martinek J, Kren V. Microphthalmia and cataract in rats with a novel point mutation in connexin 50 - L7Q. Mol Vis. 2008;14:823–8.
Yamashita S, Furumoto K, Nobukiyo A, Kamohara M, Ushijima T, Furukawa T. Mapping of A gene responsible for cataract formation and its modifier in the UPL rat. Invest Ophthalmol Vis Sci. 2002;43(10):3153–9.
Mori M, Li G, Abe I, Nakayama J, Guo Z, Sawashita J, et al. Lanosterol synthase mutations cause cholesterol deficiency-associated cataracts in the Shumiya cataract rat. J Clin Invest. 2006;116(2):395–404.
Zhao L, Chen XJ, Zhu J, Xi YB, Yang X, Hu LD, et al. Lanosterol reverses protein aggregation in cataracts. Nature. 2015;523(7562):607–11.
Watanabe K, Wada K, Ohashi T, Okubo S, Takekuma K, Hashizume R, et al. A 5-bp insertion in Mip causes recessive congenital cataract in KFRS4/Kyo rats. PLoS One. 2012;7(11):e50737.
Mori M, Nishikawa T, Higuchi K, Nishimura M. Deletion in the beige gene of the beige rat owing to recombination between LINE1s. Mamm Genome. 1999;10(7):692–5.
Kuramoto T, Kuwamura M, Serikawa T. Rat neurological mutations cerebellar vermis defect and hobble are caused by mutations in the netrin-1 receptor gene Unc5h3. Brain Res Mol Brain Res. 2004;122(2):103–8.
Mashimo T, Kaneko T, Sakuma T, Kobayashi J, Kunihiro Y, Voigt B, et al. Efficient gene targeting by TAL effector nucleases coinjected with exonucleases in zygotes. Sci Rep. 2013;3:1253.
Blaszczyk WM, Arning L, Hoffmann KP, Epplen JT. A Tyrosinase missense mutation causes albinism in the Wistar rat. Pigment Cell Res. 2005;18(2):144–5.
Kuramoto T, Yokoe M, Yagasaki K, Kawaguchi T, Kumafuji K, Serikawa T. Genetic analyses of fancy rat-derived mutations. Exp Anim. 2010;59(2):147–55.
Yoshimi K, Kaneko T, Voigt B, Mashimo T. Allele-specific genome editing and correction of disease-associated phenotypes in rats using the CRISPR-Cas platform. Nat Commun. 2014;5:4240.
Kuramoto T, Nomoto T, Sugimura T, Ushijima T. Cloning of the rat agouti gene and identification of the rat nonagouti mutation. Mamm Genome. 2001;12(6):469–71.
Yoshihara M, Sato T, Saito D, Ohara O, Kuramoto T, Suyama M. A deletion in the intergenic region upstream of Ednrb causes head spot in the rat strain KFRS4/Kyo. BMC Genet. 2017;18(1):29.
Kuramoto T, Nakanishi S, Ochiai M, Nakagama H, Voigt B, Serikawa T. Origins of albino and hooded rats: implications from molecular genetic analysis across modern laboratory rat strains. PLoS One. 2012;7(8):e43059.
Xu Y, Wu Z, Liu L, Liu J, Wang Y. Rat model of Cockayne syndrome neurological disease. Cell Rep. 2019;29(4):800–9.e5.
Gu Y, Wang L, Zhou J, Guo Q, Liu N, Ding Z, et al. A naturally-occurring mutation in Cacna1f in a rat model of congenital stationary night blindness. Mol Vis. 2008;14:20–8.
Yokoi N, Namae M, Wang HY, Kojima K, Fuse M, Yasuda K, et al. Rat neurological disease creeping is caused by a mutation in the reelin gene. Brain Res Mol Brain Res. 2003;112(1–2):1–7.
Tuggle KL, Birket SE, Cui X, Hong J, Warren J, Reid L, et al. Characterization of defects in ion transport and tissue development in cystic fibrosis transmembrane conductance regulator (CFTR)-knockout rats. PLoS One. 2014;9(3):e91253.
Dreano E, Bacchetta M, Simonin J, Galmiche L, Usal C, Slimani L, et al. Characterization of two rat models of cystic fibrosis-KO and F508del CFTR-generated by Crispr-Cas9. Animal Model Exp Med. 2019;2(4):297–311.
Sinkevicius KW, Morrison TR, Kulkarni P, Caffrey Cagliostro MK, Iriah S, Malmberg S, et al. RNaseT2 knockout rats exhibit hippocampal neuropathology and deficits in memory. Dis Model Mech. 2018;11(6):dmm032631.
Shimizu Y, Yanobu-Takanashi R, Nakano K, Hamase K, Shimizu T, Okamura T. A deletion in the Ctns gene causes renal tubular dysfunction and cystine accumulation in LEA/Tohm rats. Mamm Genome. 2019;30(1–2):23–33.
Ma S, Zhang M, Zhang S, Wang J, Zhou X, Guo G, et al. Characterisation of Lamp2-deficient rats for potential new animal model of Danon disease. Sci Rep. 2018;8(1):6932.
Shimizu Y, Ishii C, Yanobu-Takanashi R, Nakano K, Imaike A, Mita M, et al. d-Amino acid oxidase deficiency is caused by a large deletion in the Dao gene in LEA rats. Biochim Biophys Acta Proteins Proteom. 1868;2020(9):140463.
Gohma H, Kuramoto T, Kuwamura M, Okajima R, Tanimoto N, Yamasaki K, et al. WTC deafness Kyoto (dfk): a rat model for extensive investigations of Kcnq1 functions. Physiol Genomics. 2006;24(3):198–206.
Smits BM, Peters TA, Mul JD, Croes HJ, Fransen JA, Beynon AJ, et al. Identification of a rat model for usher syndrome type 1B by N-ethyl-N-nitrosourea mutagenesis-driven forward genetics. Genetics. 2005;170(4):1887–96.
Naoi K, Kuramoto T, Kuwamura Y, Gohma H, Kuwamura M, Serikawa T. Characterization of the Kyoto circling (KCI) rat carrying a spontaneous nonsense mutation in the protocadherin 15 (Pcdh15) gene. Exp Anim. 2009;58(1):1–10.
Held N, Smits BM, Gockeln R, Schubert S, Nave H, Northrup E, et al. A mutation in Myo15 leads to Usher-like symptoms in LEW/Ztm-ci2 rats. PLoS One. 2011;6(3):e15669.
Nishitani A, Tanaka M, Shimizu S, Kunisawa N, Yokoe M, Yoshida Y, et al. Involvement of aspartoacylase in tremor expression in rats. Exp Anim. 2016;65(3):293–301.
O'Connor LT, Goetz BD, Kwiecien JM, Delaney KH, Fletch AL, Duncan ID. Insertion of a retrotransposon in Mbp disrupts mRNA splicing and myelination in a new mutant rat. J Neurosci. 1999;19(9):3404–13.
Kuramoto T, Kuwamura M, Tokuda S, Izawa T, Nakane Y, Kitada K, et al. A mutation in the gene encoding mitochondrial Mg(2)+ channel MRS2 results in demyelination in the rat. PLoS Genet. 2011;7(1):e1001262.
Boison D, Stoffel W. Myelin-deficient rat: a point mutation in exon III (A----C, Thr75----Pro) of the myelin proteolipid protein causes dysmyelination and oligodendrocyte death. EMBO J. 1989;8(11):3295–302.
Duncan ID, Bugiani M, Radcliff AB, Moran JJ, Lopez-Anido C, Duong P, et al. A mutation in the Tubb4a gene leads to microtubule accumulation with hypomyelination and demyelination. Ann Neurol. 2017;81(5):690–702.
Geddes BJ, Harding TC, Lightman SL, Uney JB. Long-term gene therapy in the CNS: reversal of hypothalamic diabetes insipidus in the Brattleboro rat by using an adenovirus expressing arginine vasopressin. Nat Med. 1997;3(12):1402–4.
Schmale H, Richter D. Single base deletion in the vasopressin gene is the cause of diabetes insipidus in Brattleboro rats. Nature. 1984;308:705–9.
Mamenko M, Dhande I, Tomilin V, Zaika O, Boukelmoune N, Zhu Y, et al. Defective store-operated calcium entry causes partial nephrogenic diabetes insipidus. J Am Soc Nephrol. 2016;27(7):2035–48.
Takagishi Y, Murata Y. Myosin Va mutation in rats is an animal model for the human hereditary neurological disease, Griscelli syndrome type 1. Ann N Y Acad Sci. 2006;1086:66–80.
Landrock KK, Sullivan P, Martini-Stoica H, Goldstein DS, Graham BH, Yamamoto S, et al. Pleiotropic neuropathological and biochemical alterations associated with Myo5a mutation in a rat model. Brain Res. 1679;2018:155–70.
Larcher T, Lafoux A, Tesson L, Remy S, Thepenier V, Francois V, et al. Characterization of dystrophin deficient rats: a new model for Duchenne muscular dystrophy. PLoS One. 2014;9(10):e110371.
Nakamura K, Fujii W, Tsuboi M, Tanihata J, Teramoto N, Takeuchi S, et al. Generation of muscular dystrophy model rats with a CRISPR/Cas system. Sci Rep. 2014;4:5635.
Clifford PS, Rodriguez J, Schul D, Hughes S, Kniffin T, Hart N, et al. Attenuation of cocaine-induced locomotor sensitization in rats sustaining genetic or pharmacologic antagonism of ghrelin receptors. Addict Biol. 2012;17(6):956–63.
Chu X, Zhang Z, Yabut J, Horwitz S, Levorse J, Li XQ, et al. Characterization of multidrug resistance 1a/P-glycoprotein knockout rats generated by zinc finger nucleases. Mol Pharmacol. 2012;81(2):220–7.
Zamek-Gliszczynski MJ, Bedwell DW, Bao JQ, Higgins JW. Characterization of SAGE Mdr1a (P-gp), Bcrp, and Mrp2 knockout rats using loperamide, paclitaxel, sulfasalazine, and carboxydichlorofluorescein pharmacokinetics. Drug Metab Dispos. 2012;40(9):1825–33.
Fuchs H, Kishimoto W, Gansser D, Tanswell P, Ishiguro N. Brain penetration of WEB 2086 (Apafant) and dantrolene in Mdr1a (P-glycoprotein) and Bcrp knockout rats. Drug Metab Dispos. 2014;42(10):1761–5.
Liu X, Cheong J, Ding X, Deshmukh G. Use of cassette dosing approach to examine the effects of P-glycoprotein on the brain and cerebrospinal fluid concentrations in wild-type and P-glycoprotein knockout rats. Drug Metab Dispos. 2014;42(4):482–91.
Wei Y, Yang L, Zhang X, Sui D, Wang C, Wang K, et al. Generation and characterization of a CYP2C11-null rat model by using the CRISPR/Cas9 method. Drug Metab Dispos. 2018;46(5):525–31.
Wang RL, Xia QQ, Baerson SR, Ren Y, Wang J, Su YJ, et al. A novel cytochrome P450 CYP6AB14 gene in Spodoptera litura (Lepidoptera: Noctuidae) and its potential role in plant allelochemical detoxification. J Insect Physiol. 2015;75:54–62.
Lu J, Shao Y, Qin X, Liu D, Chen A, Li D, et al. CRISPR knockout rat cytochrome P450 3A1/2 model for advancing drug metabolism and pharmacokinetics research. Sci Rep. 2017;7:42922.
Takeuchi T, Suzuki H, Sakurai S, Nogami H, Okuma S, Ishikawa H. Molecular mechanism of growth hormone (GH) deficiency in the spontaneous dwarf rat: detection of abnormal splicing of GH messenger ribonucleic acid by the polymerase chain reaction. Endocrinology. 1990;126(1):31–8.
Chikuda H, Kugimiya F, Hoshi K, Ikeda T, Ogasawara T, Shimoaka T, et al. Cyclic GMP-dependent protein kinase II is a molecular switch from proliferation to hypertrophic differentiation of chondrocytes. Genes Dev. 2004;18(19):2418–29.
Bonnet C, Andrieux J, Beri-Dexheimer M, Leheup B, Boute O, Manouvrier S, et al. Microdeletion at chromosome 4q21 defines a new emerging syndrome with marked growth restriction, mental retardation and absent or severely delayed speech. J Med Genet. 2010;47(6):377–84.
Tsuchida A, Yokoi N, Namae M, Fuse M, Masuyama T, Sasaki M, et al. Phenotypic characterization of the Komeda miniature rat Ishikawa, an animal model of dwarfism caused by a mutation in Prkg2. Comp Med. 2008;58(6):560–7.
Hishinuma A, Furudate S, Oh-Ishi M, Nagakubo N, Namatame T, Ieiri T. A novel missense mutation (G2320R) in thyroglobulin causes hypothyroidism in rdw rats. Endocrinology. 2000;141(11):4050–5.
Furudate S, Ono M, Shibayama K, Ohyama Y, Kuwada M, Kimura T, et al. Rescue from dwarfism by thyroid function compensation in rdw rats. Exp Anim. 2005;54(5):455–60.
Yu-Taeger L, Ott T, Bonsi P, Tomczak C, Wassouf Z, Martella G, et al. Impaired dopamine- and adenosine-mediated signaling and plasticity in a novel rodent model for DYT25 dystonia. Neurobiol Dis. 2020;134:104634.
Quina LA, Kuramoto T, Luquetti DV, Cox TC, Serikawa T, Turner EE. Deletion of a conserved regulatory element required for Hmx1 expression in craniofacial mesenchyme in the dumbo rat: a newly identified cause of congenital ear malformation. Dis Model Mech. 2012;5(6):812–22.
Mori M, Li G, Hashimoto M, Nishio A, Tomozawa H, Suzuki N, et al. Pivotal advance: eosinophilia in the MES rat strain is caused by a loss-of-function mutation in the gene for cytochrome b(−245), alpha polypeptide (Cyba). J Leukoc Biol. 2009;86(3):473–8.
Sarkisian MR, Li W, Di Cunto F, D’Mello SR, LoTurco JJ. Citron-kinase, a protein essential to cytokinesis in neuronal progenitors, is deleted in the flathead mutant rat. J Neurosci. 2002;22(8):RC217.
Sarkisian MR, Rattan S, D’Mello SR, LoTurco JJ. Characterization of seizures in the flathead rat: a new genetic model of epilepsy in early postnatal development. Epilepsia. 1999;40(4):394–400.
Thomas AM, Schwartz MD, Saxe MD, Kilduff TS. Cntnap2 knockout rats and mice exhibit epileptiform activity and abnormal sleep-wake physiology. Sleep. 2017;40(1):zsw026.
Ishida S, Sakamoto Y, Nishio T, Baulac S, Kuwamura M, Ohno Y, et al. Kcna1-mutant rats dominantly display myokymia, neuromyotonia and spontaneous epileptic seizures. Brain Res. 2012;1435:154–66.
Baulac S, Ishida S, Mashimo T, Boillot M, Fumoto N, Kuwamura M, et al. A rat model for LGI1-related epilepsies. Hum Mol Genet. 2012;21(16):3546–57.
Kinboshi M, Shimizu S, Mashimo T, Serikawa T, Ito H, Ikeda A, et al. Down-regulation of astrocytic Kir4.1 channels during the audiogenic epileptogenesis in Leucine-Rich Glioma-Inactivated 1 (Lgi1) mutant rats. Int J Mol Sci. 2019;20(5):1013.
Mashimo T, Ohmori I, Ouchida M, Ohno Y, Tsurumi T, Miki T, et al. A missense mutation of the gene encoding voltage-dependent sodium channel (Nav1.1) confers susceptibility to febrile seizures in rats. J Neurosci. 2010;30(16):5744–53.
Tokudome K, Okumura T, Shimizu S, Mashimo T, Takizawa A, Serikawa T, et al. Synaptic vesicle glycoprotein 2A (SV2A) regulates kindling epileptogenesis via GABAergic neurotransmission. Sci Rep. 2016;6:27420.
Suzuki H, Katayama K, Takenaka M, Amakasu K, Saito K, Suzuki K. A spontaneous mutation of the Wwox gene and audiogenic seizures in rats with lethal dwarfism and epilepsy. Genes Brain Behav. 2009;8(7):650–60.
Miller JJ, Aoki K, Moehring F, Murphy CA, O’Hara CL, Tiemeyer M, et al. Neuropathic pain in a Fabry disease rat model. JCI Insight. 2018;3(6):e99171.
Bulbul M, Babygirija R, Zheng J, Ludwig K, Xu H, Lazar J, et al. Food intake and interdigestive gastrointestinal motility in ghrelin receptor mutant rats. J Gastroenterol. 2011;46(4):469–78.
MacKay H, Charbonneau VR, St-Onge V, Murray E, Watts A, Wellman MK, et al. Rats with a truncated ghrelin receptor (GHSR) do not respond to ghrelin, and show reduced intake of palatable, high-calorie food. Physiol Behav. 2016;163:88–96.
Zallar LJ, Tunstall BJ, Richie CT, Zhang YJ, You ZB, Gardner EL, et al. Development and initial characterization of a novel ghrelin receptor CRISPR/Cas9 knockout wistar rat model. Int J Obes. 2019;43(2):344–54.
Tian Y, Yang C, Shang S, Cai Y, Deng X, Zhang J, et al. Loss of FMRP impaired hippocampal long-term plasticity and spatial learning in rats. Front Mol Neurosci. 2017;10:269.
Berzhanskaya J, Phillips MA, Shen J, Colonnese MT. Sensory hypo-excitability in a rat model of fetal development in Fragile X Syndrome. Sci Rep. 2016;6:30769.
Golden CEM, Breen MS, Koro L, Sonar S, Niblo K, Browne A, et al. Deletion of the KH1 domain of Fmr1 leads to transcriptional alterations and attentional deficits in rats. Cereb Cortex. 2019;29(5):2228–44.
Kiyozumi D, Nakano I, Takahashi KL, Hojo H, Aoyama H, Sekiguchi K. Fused pulmonary lobes is a rat model of human Fraser syndrome. Biochem Biophys Res Commun. 2011;411(2):440–4.
Maichele AJ, Burwinkel B, Maire I, Sovik O, Kilimann MW. Mutations in the testis/liver isoform of the phosphorylase kinase gamma subunit (PHKG2) cause autosomal liver glycogenosis in the gsd rat and in humans. Nat Genet. 1996;14(3):337–40.
Kuramoto T, Kuwamura M, Tagami F, Mashimo T, Nose M, Serikawa T. Kyoto rhino rats derived by ENU mutagenesis undergo congenital hair loss and exhibit focal glomerulosclerosis. Exp Anim. 2011;60(1):57–63.
Nanashima N, Akita M, Yamada T, Shimizu T, Nakano H, Fan Y, et al. The hairless phenotype of the Hirosaki hairless rat is due to the deletion of an 80-kb genomic DNA containing five basic keratin genes. J Biol Chem. 2008;283(24):16868–75.
Kuramoto T, Hirano R, Kuwamura M, Serikawa T. Identification of the rat rex mutation as a 7-bp deletion at splicing acceptor site of the Krt71 gene. J Vet Med Sci. 2010;72(7):909–12.
Ahearn K, Akkouris G, Berry PR, Chrissluis RR, Crooks IM, Dull AK, et al. The Charles River “hairless” rat mutation maps to chromosome 1: allelic with fuzzy and a likely orthologue of mouse frizzy. J Hered. 2002;93(3):210–3.
Spacek DV, Perez AF, Ferranti KM, Wu LK, Moy DM, Magnan DR, et al. The mouse frizzy (fr) and rat ‘hairless’ (frCR) mutations are natural variants of protease serine S1 family member 8 (Prss8). Exp Dermatol. 2010;19(6):527–32.
Asakawa M, Yoshioka T, Matsutani T, Hikita I, Suzuki M, Oshima I, et al. Association of a mutation in TRPV3 with defective hair growth in rodents. J Invest Dermatol. 2006;126(12):2664–72.
Bartnikas TB, Wildt SJ, Wineinger AE, Schmitz-Abe K, Markianos K, Cooper DM, et al. A novel rat model of hereditary hemochromatosis due to a mutation in transferrin receptor 2. Comp Med. 2013;63(2):143–55.
Booth CJ, Brooks MB, Rockwell S, Murphy JW, Rinder HM, Zelterman D, et al. WAG-F8(m1Ycb) rats harboring a factor VIII gene mutation provide a new animal model for hemophilia A. J Thromb Haemost. 2010;8(11):2472–7.
Nielsen LN, Wiinberg B, Hager M, Holmberg HL, Hansen JJ, Roepstorff K, et al. A novel F8 −/− rat as a translational model of human hemophilia A. J Thromb Haemost. 2014;12(8):1274–82.
Sorensen KR, Roepstorff K, Wiinberg B, Hansen AK, Tranholm M, Nielsen LN, et al. The F8(−/−) rat as a model of hemophilic arthropathy. J Thromb Haemost. 2016;14(6):1216–25.
Shi Q, Mattson JG, Fahs SA, Geurts AM, Weiler H, Montgomery RR. The severe spontaneous bleeding phenotype in a novel hemophilia a rat model is rescued by platelet FVIII expression. Blood Adv. 2020;4(1):55–65.
Zhang L, Shao Y, Li L, Tian F, Cen J, Chen X, et al. Efficient liver repopulation of transplanted hepatocyte prevents cirrhosis in a rat model of hereditary tyrosinemia type I. Sci Rep. 2016;6:31460.
Shao Y, Wang L, Guo N, Wang S, Yang L, Li Y, et al. Cas9-nickase-mediated genome editing corrects hereditary tyrosinemia in rats. J Biol Chem. 2018;293(18):6883–92.
Oiso N, Riddle SR, Serikawa T, Kuramoto T, Spritz RA. The rat Ruby ( R) locus is Rab38: identical mutations in Fawn-hooded and Tester-Moriyama rats derived from an ancestral Long Evans rat sub-strain. Mamm Genome. 2004;15(4):307–14.
Osanai K, Higuchi J, Oikawa R, Kobayashi M, Tsuchihara K, Iguchi M, et al. Altered lung surfactant system in a Rab38-deficient rat model of Hermansky-Pudlak syndrome. Am J Physiol Lung Cell Mol Physiol. 2010;298(2):L243–51.
Emmert AS, Iwasawa E, Shula C, Schultz P, Lindquist D, Dunn RS, et al. Impaired neural differentiation and glymphatic CSF flow in the Ccdc39 rat model of neonatal hydrocephalus: genetic interaction with L1cam. Dis Model Mech. 2019;12(11):dmm040972 https://doi.org/10.1242/dmm.040972.
Konishi S, Tanaka N, Mashimo T, Yamamoto T, Sakuma T, Kaneko T, et al. Pathological characteristics of Ccdc85c knockout rats: a rat model of genetic hydrocephalus. Exp Anim. 2020;69(1):26–33.
Emmert AS, Vuong SM, Shula C, Lindquist D, Yuan W, Hu YC, et al. Characterization of a novel rat model of X-linked hydrocephalus by CRISPR-mediated mutation in L1cam. J Neurosurg. 2019:1–14.
Wada M, Toh S, Taniguchi K, Nakamura T, Uchiumi T, Kohno K, et al. Mutations in the canilicular multispecific organic anion transporter (cMOAT) gene, a novel ABC transporter, in patients with hyperbilirubinemia II/Dubin-Johnson syndrome. Hum Mol Genet. 1998;7(2):203–7.
Paulusma CC, Bosma PJ, Zaman GJ, Bakker CT, Otter M, Scheffer GL, et al. Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene. Science. 1996;271(5252):1126–8.
Ito K, Suzuki H, Hirohashi T, Kume K, Shimizu T, Sugiyama Y. Molecular cloning of canalicular multispecific organic anion transporter defective in EHBR. Am J Phys. 1997;272(1 Pt 1):G16–22.
Ma X, Shang X, Qin X, Lu J, Liu M, Wang X. Characterization of organic anion transporting polypeptide 1b2 knockout rats generated by CRISPR/Cas9: a novel model for drug transport and hyperbilirubinemia disease. Acta Pharm Sin B. 2020;10(5):850–60.
Iyanagi T. Molecular basis of multiple UDP-glucuronosyltransferase isoenzyme deficiencies in the hyperbilirubinemic rat (Gunn rat). J Biol Chem. 1991;266(35):24048–52.
Takahashi M, Ilan Y, Chowdhury NR, Guida J, Horwitz M, Chowdhury JR. Long term correction of bilirubin-UDP-glucuronosyltransferase deficiency in Gunn rats by administration of a recombinant adenovirus during the neonatal period. J Biol Chem. 1996;271(43):26536–42.
Zhao Y, Yang Y, Xing R, Cui X, Xiao Y, Xie L, et al. Hyperlipidemia induces typical atherosclerosis development in Ldlr and Apoe deficient rats. Atherosclerosis. 2018;271:26–35.
Phillips EH, Chang MS, Gorman S, Qureshi HJ, Ejendal KFK, Kinzer-Ursem TL, et al. Angiotensin infusion does not cause abdominal aortic aneurysms in apolipoprotein E-deficient rats. J Vasc Res. 2018;55:1–12.
Lee JG, Ha CH, Yoon B, Cheong SA, Kim G, Lee DJ, et al. Knockout rat models mimicking human atherosclerosis created by Cpf1-mediated gene targeting. Sci Rep. 2019;9(1):2628.
Asahina M, Mashimo T, Takeyama M, Tozawa R, Hashimoto T, Takizawa A, et al. Hypercholesterolemia and atherosclerosis in low density lipoprotein receptor mutant rats. Biochem Biophys Res Commun. 2012;418(3):553–8.
Wang HY, Quan C, Hu C, Xie B, Du Y, Chen L, et al. A lipidomics study reveals hepatic lipid signatures associating with deficiency of the LDL receptor in a rat model. Biol Open. 2016;5(7):979–86.
Asahina M, Haruyama W, Ichida Y, Sakamoto M, Sato M, Imaizumi K. Identification of SMEK2 as a candidate gene for regulation of responsiveness to dietary cholesterol in rats. J Lipid Res. 2009;50(1):41–6.
Yu Y, Zhang N, Dong X, Fan N, Wang L, Xu Y, Chen H, Duan W. Uricase-deficient rat is generated with CRISPR/Cas9 technique. Peer J. 2020;8:e8971.
Liska F, Gosele C, Rivkin E, Tres L, Cardoso MC, Domaing P, et al. Rat hd mutation reveals an essential role of centrobin in spermatid head shaping and assembly of the head-tail coupling apparatus. Biol Reprod. 2009;81(6):1196–205.
Kuramoto T, Yokoe M, Hashimoto R, Hiai H, Serikawa T. A rat model of hypohidrotic ectodermal dysplasia carries a missense mutation in the Edaradd gene. BMC Genet. 2011;12:91.
Weber M, Wu T, Meilandt WJ, Dominguez SL, Solanoy HO, Maloney JA, et al. BACE1 across species: a comparison of the in vivo consequences of BACE1 deletion in mice and rats. Sci Rep. 2017;7:44249.
Yang J, Yi N, Zhang J, He W, He D, Wu W, et al. Generation and characterization of a hypothyroidism rat model with truncated thyroid stimulating hormone receptor. Sci Rep. 2018;8(1):4004.
Jahoda CA, Kljuic A, O'Shaughnessy R, Crossley N, Whitehouse CJ, Robinson M, et al. The lanceolate hair rat phenotype results from a missense mutation in a calcium coordinating site of the desmoglein 4 gene. Genomics. 2004;83(5):747–56.
Bazzi H, Kljuic A, Christiano AM, Christiano AM, Panteleyev AA. Intragenic deletion in the Desmoglein 4 gene underlies the skin phenotype in the Iffa Credo “hairless” rat. Differentiation. 2004;72(8):450–64.
Meyer B, Bazzi H, Zidek V, Musilova A, Pravenec M, Kurtz TW, et al. A spontaneous mutation in the desmoglein 4 gene underlies hypotrichosis in a new lanceolate hair rat model. Differentiation. 2004;72(9–10):541–7.
Menoret S, Iscache AL, Tesson L, Remy S, Usal C, Osborn MJ, et al. Characterization of immunoglobulin heavy chain knockout rats. Eur J Immunol. 2010;40(10):2932–41.
Osborn MJ, Ma B, Avis S, Binnie A, Dilley J, Yang X, et al. High-affinity IgG antibodies develop naturally in Ig-knockout rats carrying germline human IgH/Igkappa/Iglambda loci bearing the rat CH region. J Immunol. 2013;190(4):1481–90.
Nehls M, Pfeifer D, Schorpp M, Hedrich H, Boehm T. New member of the winged-helix protein family disrupted in mouse and rat nude mutations. Nature. 1994;372(6501):103–7.
Segre JA, Nemhauser JL, Taylor BA, Nadeau JH, Lander ES. Positional cloning of the nude locus: genetic, physical, and transcription maps of the region and mutations in the mouse and rat. Genomics. 1995;28(3):549–59.
Goto T, Hara H, Nakauchi H, Hochi S, Hirabayashi M. Hypomorphic phenotype of Foxn1 gene-modified rats by CRISPR/Cas9 system. Transgenic Res. 2016;25(4):533–44.
Mashimo T, Takizawa A, Kobayashi J, Kunihiro Y, Yoshimi K, Ishida S, et al. Generation and characterization of severe combined immunodeficiency rats. Cell Rep. 2012;2(3):685–94.
Beldick SR, Hong J, Altamentova S, Khazaei M, Hundal A, Zavvarian MM, et al. Severe-combined immunodeficient rats can be used to generate a model of perinatal hypoxic-ischemic brain injury to facilitate studies of engrafted human neural stem cells. PLoS One. 2018;13(11):e0208105.
Zschemisch NH, Glage S, Wedekind D, Weinstein EJ, Cui X, Dorsch M, et al. Zinc-finger nuclease mediated disruption of Rag1 in the LEW/Ztm rat. BMC Immunol. 2012;13:60.
Noto FK, Adjan-Steffey V, Tong M, Ravichandran K, Zhang W, Arey A, et al. Sprague Dawley Rag2-null rats created from engineered spermatogonial stem cells are immunodeficient and permissive to human xenografts. Mol Cancer Ther. 2018;17(11):2481–9.
He D, Zhang J, Wu W, Yi N, He W, Lu P, et al. A novel immunodeficient rat model supports human lung cancer xenografts. FASEB J. 2019;33(1):140–50.
Mashimo T, Takizawa A, Voigt B, Yoshimi K, Hiai H, Kuramoto T, et al. Generation of knockout rats with X-linked severe combined immunodeficiency (X-SCID) using zinc-finger nucleases. PLoS One. 2010;5(1):e8870.
Menoret S, Ouisse LH, Tesson L, Delbos F, Garnier D, Remy S, et al. Generation of Immunodeficient rats with Rag1 and Il2rg gene deletions and human tissue grafting models. Transplantation. 2018;102(8):1271–8.
Abdul-Majeed S, Mell B, Nauli SM, Joe B. Cryptorchidism and infertility in rats with targeted disruption of the Adamts16 locus. PLoS One. 2014;9(7):e100967.
Yarbrough WG, Quarmby VE, Simental JA, Joseph DR, Sar M, Lubahn DB, et al. A single base mutation in the androgen receptor gene causes androgen insensitivity in the testicular feminized rat. J Biol Chem. 1990;265(15):8893–900.
Ebihara C, Ebihara K, Aizawa-Abe M, Mashimo T, Tomita T, Zhao M, et al. Seipin is necessary for normal brain development and spermatogenesis in addition to adipogenesis. Hum Mol Genet. 2015;24(15):4238–49.
Zhang C, Zhou Y, Xie S, Yin Q, Tang C, Ni Z, et al. CRISPR/Cas9-mediated genome editing reveals the synergistic effects of beta-defensin family members on sperm maturation in rat epididymis. FASEB J. 2018;32(3):1354–63.
Kawai Y, Noguchi J, Akiyama K, Takeno Y, Fujiwara Y, Kajita S, et al. A missense mutation of the Dhh gene is associated with male pseudohermaphroditic rats showing impaired Leydig cell development. Reproduction. 2011;141(2):217–25.
Rumi MA, Dhakal P, Kubota K, Chakraborty D, Lei T, Larson MA, et al. Generation of Esr1-knockout rats using zinc finger nuclease-mediated genome editing. Endocrinology. 2014;155(5):1991–9.
MAK R, Singh P, Roby KF, Zhao X, Iqbal K, Ratri A, et al. Defining the role of estrogen receptor beta in the regulation of female fertility. Endocrinology. 2017;158(7):2330–43.
Khristi V, Chakravarthi VP, Singh P, Ghosh S, Pramanik A, Ratri A, et al. ESR2 regulates granulosa cell genes essential for follicle maturation and ovulation. Mol Cell Endocrinol. 2018;474:214–26.
Khristi V, Ghosh S, Chakravarthi VP, Wolfe MW, Rumi MAK. Transcriptome data analyses of prostatic hyperplasia in Esr2 knockout rats. Data Brief. 2019;24:103826.
Uenoyama Y, Nakamura S, Hayakawa Y, Ikegami K, Watanabe Y, Deura C, et al. Lack of pulse and surge modes and glutamatergic stimulation of luteinising hormone release in Kiss1 knockout rats. J Neuroendocrinol. 2015;27(3):187–97.
Kobayashi T, Kobayashi H, Goto T, Takashima T, Oikawa M, Ikeda H, et al. Germline development in rat revealed by visualization and deletion of Prdm14. Development. 2020;147(4):dev183798.
Liska F, Chylikova B, Janku M, Seda O, Vernerova Z, Pravenec M, et al. Splicing mutation in Sbf1 causes nonsyndromic male infertility in the rat. Reproduction. 2016;152(3):215–23.
Ishishita S, Inui T, Matsuda Y, Serikawa T, Kitada K. Infertility associated with meiotic failure in the tremor rat (tm/tm) is caused by the deletion of spermatogenesis associated 22. Exp Anim. 2013;62(3):219–27.
Hayashi I, Hoshiko S, Makabe O, Oh-ishi S. A point mutation of alanine 163 to threonine is responsible for the defective secretion of high molecular weight kininogen by the liver of brown Norway Katholiek rats. J Biol Chem. 1993;268(23):17219–24.
Kaschina E, Stoll M, Sommerfeld M, Steckelings UM, Kreutz R, Unger T. Genetic kininogen deficiency contributes to aortic aneurysm formation but not to atherosclerosis. Physiol Genomics. 2004;19(1):41–9.
Mul JD, Nadra K, Jagalur NB, Nijman IJ, Toonen PW, Medard JJ, et al. A hypomorphic mutation in Lpin1 induces progressively improving neuropathy and lipodystrophy in the rat. J Biol Chem. 2011;286(30):26781–93.
Chabod M, Pedros C, Lamouroux L, Colacios C, Bernard I, Lagrange D, et al. A spontaneous mutation of the rat Themis gene leads to impaired function of regulatory T cells linked to inflammatory bowel disease. PLoS Genet. 2012;8(1):e1002461.
Shaheen R, Hashem A, Abdel-Salam GM, Al-Fadhli F, Ewida N, Alkuraya FS. Mutations in CIT, encoding citron rho-interacting serine/threonine kinase, cause severe primary microcephaly in humans. Hum Genet. 2016;135(10):1191–7.
van Boxtel R, Vroling B, Toonen P, Nijman IJ, van Roekel H, Verheul M, et al. Systematic generation of in vivo G protein-coupled receptor mutants in the rat. Pharmacogenomics J. 2011;11(5):326–36.
Marsan E, Ishida S, Schramm A, Weckhuysen S, Muraca G, Lecas S, et al. Depdc5 knockout rat: a novel model of mTORopathy. Neurobiol Dis. 2016;89:180–9.
Kunieda T, Simonaro CM, Yoshida M, Ikadai H, Levan G, Desnick RJ, et al. Mucopolysaccharidosis type VI in rats: isolation of cDNAs encoding arylsulfatase B, chromosomal localization of the gene, and identification of the mutation. Genomics. 1995;29(3):582–7.
Eliyahu E, Wolfson T, Ge Y, Jepsen KJ, Schuchman EH, Simonaro CM. Anti-TNF-alpha therapy enhances the effects of enzyme replacement therapy in rats with mucopolysaccharidosis type VI. PLoS One. 2011;6(8):e22447.
Yang X, Lu D, Zhang X, Chen W, Gao S, Dong W, et al. Knockout of ISCA1 causes early embryonic death in rats. Animal Model Exp Med. 2019;2(1):18–24.
Fan F, Geurts AM, Pabbidi MR, Smith SV, Harder DR, Jacob H, et al. Zinc-finger nuclease knockout of dual-specificity protein phosphatase-5 enhances the myogenic response and autoregulation of cerebral blood flow in FHH.1BN rats. PLoS One. 2014;9(11):e112878.
Zigler JS Jr, Hodgkinson CA, Wright M, Klise A, Sundin O, Broman KW, et al. A spontaneous missense mutation in branched chain Keto acid dehydrogenase kinase in the rat affects both the central and peripheral nervous systems. PLoS One. 2016;11(7):e0160447.
Xu J, Zhang L, Xie M, Li Y, Huang P, Saunders TL, et al. Role of complement in a rat model of paclitaxel-induced peripheral neuropathy. J Immunol. 2018;200(12):4094–101.
Asahina M, Fujinawa R, Nakamura S, Yokoyama K, Tozawa R, Suzuki T. Ngly1−/− rats develop neurodegenerative phenotypes and pathological abnormalities in their peripheral and central nervous systems. Hum Mol Genet. 2020.
Wiedemann T, Bielohuby M, Muller TD, Bidlingmaier M, Pellegata NS. Obesity in MENX rats is accompanied by high circulating levels of ghrelin and improved insulin sensitivity. Diabetes. 2016;65(2):406–20.
Aizawa-Abe M, Ebihara K, Ebihara C, Mashimo T, Takizawa A, Tomita T, et al. Generation of leptin-deficient Lepmkyo/Lepmkyo rats and identification of leptin-responsive genes in the liver. Physiol Genomics. 2013;45(17):786–93.
Vaira S, Yang C, McCoy A, Keys K, Xue S, Weinstein EJ, et al. Creation and preliminary characterization of a leptin knockout rat. Endocrinology. 2012;153(11):5622–8.
Wu-Peng XS, Chua SC Jr, Okada N, Liu SM, Nicolson M, Leibel RL. Phenotype of the obese Koletsky (f) rat due to Tyr763Stop mutation in the extracellular domain of the leptin receptor (Lepr): evidence for deficient plasma-to-CSF transport of leptin in both the Zucker and Koletsky obese rat. Diabetes. 1997;46(3):513–8.
Chua SC Jr, White DW, Wu-Peng XS, Liu SM, Okada N, Kershaw EE, et al. Phenotype of fatty due to Gln269Pro mutation in the leptin receptor (Lepr). Diabetes. 1996;45(8):1141–3.
Bao D, Ma Y, Zhang X, Guan F, Chen W, Gao K, et al. Preliminary characterization of a leptin receptor knockout rat created by CRISPR/Cas9 system. Sci Rep. 2015;5:15942.
Mul JD, van Boxtel R, Bergen DJ, Brans MA, Brakkee JH, Toonen PW, et al. Melanocortin receptor 4 deficiency affects body weight regulation, grooming behavior, and substrate preference in the rat. Obesity (Silver Spring). 2012;20(3):612–21.
Katayama K, Sasaki T, Goto S, Ogasawara K, Maru H, Suzuki K, et al. Insertional mutation in the Golgb1 gene is associated with osteochondrodysplasia and systemic edema in the OCD rat. Bone. 2011;49(5):1027–36.
Van Wesenbeeck L, Odgren PR, Coxon FP, Frattini A, Moens P, Perdu B, et al. Involvement of PLEKHM1 in osteoclastic vesicular transport and osteopetrosis in incisors absent rats and humans. J Clin Invest. 2007;117(4):919–30.
Ubels JL, Diegel CR, Foxa GE, Ethen NJ, Lensing JN, Madaj ZB, et al. Low-density lipoprotein receptor-related protein 5 (LRP5)-deficient rats have reduced bone mass and abnormal development of the retinal vasculature. bioRxiv. 2020.
Baptista MA, Dave KD, Frasier MA, Sherer TB, Greeley M, Beck MJ, et al. Loss of leucine-rich repeat kinase 2 (LRRK2) in rats leads to progressive abnormal phenotypes in peripheral organs. PLoS One. 2013;8(11):e80705.
Ness D, Ren Z, Gardai S, Sharpnack D, Johnson VJ, Brennan RJ, et al. Leucine-rich repeat kinase 2 (LRRK2)-deficient rats exhibit renal tubule injury and perturbations in metabolic and immunological homeostasis. PLoS One. 2013;8(6):e66164.
Rouillard C, Baillargeon J, Paquet B, St-Hilaire M, Maheux J, Levesque C, et al. Genetic disruption of the nuclear receptor Nur77 (Nr4a1) in rat reduces dopamine cell loss and l-Dopa-induced dyskinesia in experimental Parkinson's disease. Exp Neurol. 2018;304:143–53.
Sun J, Kouranova E, Cui X, Mach RH, Xu J. Regulation of dopamine presynaptic markers and receptors in the striatum of DJ-1 and Pink1 knockout rats. Neurosci Lett. 2013;557 Pt B:123–8.
Dave KD, De Silva S, Sheth NP, Ramboz S, Beck MJ, Quang C, et al. Phenotypic characterization of recessive gene knockout rat models of Parkinson’s disease. Neurobiol Dis. 2014;70:190–203.
Villeneuve LM, Purnell PR, Boska MD, Fox HS. Early expression of Parkinson’s disease-related mitochondrial abnormalities in PINK1 knockout rats. Mol Neurobiol. 2016;53(1):171–86.
Guatteo E, Rizzo FR, Federici M, Cordella A, Ledonne A, Latini L, et al. Functional alterations of the dopaminergic and glutamatergic systems in spontaneous alpha-synuclein overexpressing rats. Exp Neurol. 2017;287(Pt 1):21–33.
Stoica G, Lungu G, Bjorklund NL, Taglialatela G, Zhang X, Chiu V, et al. Potential role of alpha-synuclein in neurodegeneration: studies in a rat animal model. J Neurochem. 2012;122(4):812–22.
Kuramoto T, Gohma H, Kimura K, Wedekind D, Hedrich HJ, Serikawa T. The rat pink-eyed dilution (p) mutation: an identical intragenic deletion in pink-eye dilute-coat strains and several Wistar-derived albino strains. Mamm Genome. 2005;16(9):712–9.
Brown JH, Bihoreau MT, Hoffmann S, Kranzlin B, Tychinskaya I, Obermuller N, et al. Missense mutation in sterile alpha motif of novel protein SamCystin is associated with polycystic kidney disease in (cy/+) rat. J Am Soc Nephrol. 2005;16(12):3517–26.
Neudecker S, Walz R, Menon K, Maier E, Bihoreau MT, Obermuller N, et al. Transgenic overexpression of Anks6(p.R823W) causes polycystic kidney disease in rats. Am J Pathol. 2010;177(6):3000–9.
Hoff S, Halbritter J, Epting D, Frank V, Nguyen TM, van Reeuwijk J, et al. ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3. Nat Genet. 2013;45(8):951–6.
McCooke JK, Appels R, Barrero RA, Ding A, Ozimek-Kulik JE, Bellgard MI, et al. A novel mutation causing nephronophthisis in the Lewis polycystic kidney rat localises to a conserved RCC1 domain in Nek8. BMC Genomics. 2012;13:393.
Arkhipov SN, Potter DL, Geurts AM, Pavlov TS. Knockout of P2rx7 purinergic receptor attenuates cyst growth in a rat model of ARPKD. Am J Physiol Renal Physiol. 2019;317(6):F1649–F55.
Ward CJ, Hogan MC, Rossetti S, Walker D, Sneddon T, Wang X, et al. The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein. Nat Genet. 2002;30(3):259–69.
Smith UM, Consugar M, Tee LJ, McKee BM, Maina EN, Whelan S, et al. The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat. Nat Genet. 2006;38(2):191–6.
Liska F, Snajdr P, Sedova L, Seda O, Chylikova B, Slamova P, et al. Deletion of a conserved noncoding sequence in Plzf intron leads to Plzf down-regulation in limb bud and polydactyly in the rat. Dev Dyn. 2009;238(3):673–84.
Liska F, Peterkova R, Peterka M, Landa V, Zidek V, Mlejnek P, et al. Targeting of the Plzf gene in the rat by transcription activator-like effector nuclease results in caudal regression syndrome in spontaneously hypertensive rats. PLoS One. 2016;11(10):e0164206.
Li Q, Kingman J, van de Wetering K, Tannouri S, Sundberg JP, Uitto J. Abcc6 knockout Rat model highlights the role of liver in PPi homeostasis in pseudoxanthoma Elasticum. J Invest Dermatol. 2017;137(5):1025–32.
Yu D, Zhong Y, Li X, Li Y, Li X, Cao J, et al. Generation of TALEN-mediated FH knockout rat model. Oncotarget. 2016;7(38):61656–69.
D’Cruz PM, Yasumura D, Weir J, Matthes MT, Abderrahim H, LaVail MM, et al. Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. Hum Mol Genet. 2000;9(4):645–51.
Ostergaard E, Duno M, Batbayli M, Vilhelmsen K, Rosenberg T. A novel MERTK deletion is a common founder mutation in the Faroe Islands and is responsible for a high proportion of retinitis pigmentosa cases. Mol Vis. 2011;17:1485–92.
Vollrath D, Feng W, Duncan JL, Yasumura D, D’Cruz PM, Chappelow A, et al. Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer of Mertk. Proc Natl Acad Sci U S A. 2001;98(22):12584–9.
Zhao M, Andrieu-Soler C, Kowalczuk L, Paz Cortes M, Berdugo M, Dernigoghossian M, et al. A new CRB1 rat mutation links Muller glial cells to retinal telangiectasia. J Neurosci. 2015;35(15):6093–106.
Yeo JH, Jung BK, Lee H, Baek IJ, Sung YH, Shin HS, et al. Development of a Pde6b gene knockout rat model for studies of degenerative retinal diseases. Invest Ophthalmol Vis Sci. 2019;60(5):1519–26.
Patterson KC, Hawkins VE, Arps KM, Mulkey DK, Olsen ML. MeCP2 deficiency results in robust Rett-like behavioural and motor deficits in male and female rats. Hum Mol Genet. 2016;25(24):5514–5.
Patterson KC, Hawkins VE, Arps KM, Mulkey DK, Olsen ML. MeCP2 deficiency results in robust Rett-like behavioural and motor deficits in male and female rats. Hum Mol Genet. 2016;25(15):3303–20.
Wu Y, Zhong W, Cui N, Johnson CM, Xing H, Zhang S, et al. Characterization of Rett syndrome-like phenotypes in Mecp2-knockout rats. J Neurodev Disord. 2016;8:23.
Nishikawa M, Yasuda K, Takamatsu M, Abe K, Okamoto K, Horibe K, et al. Generation of novel genetically modified rats to reveal the molecular mechanisms of vitamin D actions. Sci Rep. 2020;10(1):5677.
Chen J, Batta A, Zheng S, Fitzgibbon WR, Ullian ME, Yu H, et al. The missense mutation in Abcg5 gene in spontaneously hypertensive rats (SHR) segregates with phytosterolemia but not hypertension. BMC Genet. 2005;6:40.
Umeda T, Takashima N, Nakagawa R, Maekawa M, Ikegami S, Yoshikawa T, et al. Evaluation of Pax6 mutant rat as a model for autism. PLoS One. 2010;5(12):e15500.
Matsuo T, Osumi-Yamashita N, Noji S, Ohuchi H, Koyama E, Myokai F, et al. A mutation in the Pax-6 gene in rat small eye is associated with impaired migration of midbrain crest cells. Nat Genet. 1993;3(4):299–304.
Abe K, Takamatsu N, Ishikawa K, Tsurumi T, Tanimoto S, Sakurai Y, et al. Novel ENU-induced mutation in Tbx6 causes dominant spondylocostal dysostosis-like vertebral malformations in the rat. PLoS One. 2015;10(6):e0130231.
Suzuki H, Ito Y, Shinohara M, Yamashita S, Ichinose S, Kishida A, et al. Gene targeting of the transcription factor Mohawk in rats causes heterotopic ossification of Achilles tendon via failed tenogenesis. Proc Natl Acad Sci U S A. 2016;113(28):7840–5.
Northrup E, Zschemisch NH, Eisenblatter R, Glage S, Wedekind D, Cuppen E, et al. The ter mutation in the rat Dnd1 gene initiates gonadal teratomas and infertility in both genders. PLoS One. 2012;7(5):e38001.
Asano A, Tsubomatsu K, Jung CG, Sasaki N, Agui T. A deletion mutation of the protein tyrosine phosphatase kappa (Ptprk) gene is responsible for T-helper immunodeficiency (thid) in the LEC rat. Mamm Genome. 2007;18(11):779–86.
Kose H, Sakai T, Tsukumo S, Wei K, Yamada T, Yasutomo K, et al. Maturational arrest of thymocyte development is caused by a deletion in the receptor-like protein tyrosine phosphatase kappa gene in LEC rats. Genomics. 2007;89(6):673–7.
Van Wesenbeeck L, Odgren PR, MacKay CA, D’Angelo M, Safadi FF, Popoff SN, et al. The osteopetrotic mutation toothless (tl) is a loss-of-function frameshift mutation in the rat Csf1 gene: evidence of a crucial role for CSF-1 in osteoclastogenesis and endochondral ossification. Proc Natl Acad Sci U S A. 2002;99(22):14303–8.
Dobbins DE, Sood R, Hashiramoto A, Hansen CT, Wilder RL, Remmers EF. Mutation of macrophage colony stimulating factor (Csf1) causes osteopetrosis in the tl rat. Biochem Biophys Res Commun. 2002;294(5):1114–20.
Taguchi K, Takaku M, Egner PA, Morita M, Kaneko T, Mashimo T, et al. Generation of a new model rat: Nrf2 knockout rats are sensitive to aflatoxin B1 toxicity. Toxicol Sci. 2016;152(1):40–52.
Newman ZL, Printz MP, Liu S, Crown D, Breen L, Miller-Randolph S, et al. Susceptibility to anthrax lethal toxin-induced rat death is controlled by a single chromosome 10 locus that includes rNlrp1. PLoS Pathog. 2010;6(5):e1000906.
Cirelli KM, Gorfu G, Hassan MA, Printz M, Crown D, Leppla SH, et al. Inflammasome sensor NLRP1 controls rat macrophage susceptibility to toxoplasma gondii. PLoS Pathog. 2014;10(3):e1003927.
Kitada K, Akimitsu T, Shigematsu Y, Kondo A, Maihara T, Yokoi N, et al. Accumulation of N-acetyl-L-aspartate in the brain of the tremor rat, a mutant exhibiting absence-like seizure and spongiform degeneration in the central nervous system. J Neurochem. 2000;74(6):2512–9.
Nishitani A, Nagayoshi H, Takenaka S, Asano M, Shimizu S, Ohno Y, et al. Involvement of NMDA receptors in tremor expression in Aspa/Hcn1 double-knockout rats. Exp Anim. 2020; https://doi.org/10.1538/expanim.20-0025.
Kuramoto T, Kitada K, Inui T, Sasaki Y, Ito K, Hase T, et al. Attractin/mahogany/zitter plays a critical role in myelination of the central nervous system. Proc Natl Acad Sci U S A. 2001;98(2):559–64.
Kuwamura M, Maeda M, Kuramoto T, Kitada K, Kanehara T, Moriyama M, et al. The myelin vacuolation (mv) rat with a null mutation in the attractin gene. Lab Investig. 2002;82(10):1279–86.
Tanaka M, Izawa T, Yamate J, Franklin RJ, Kuramoto T, Serikawa T, et al. The VF rat with abnormal myelinogenesis has a mutation in Dopey1. Glia. 2014;62(9):1530–42.
Kuramoto T, Yokoe M, Kunisawa N, Ohashi K, Miyake T, Higuchi Y, et al. Tremor dominant Kyoto (Trdk) rats carry a missense mutation in the gene encoding the SK2 subunit of small-conductance Ca(2+)-activated K(+) channel. Brain Res. 1676;2017:38–45.
Samanas NB, Commers TW, Dennison KL, Harenda QE, Kurz SG, Lachel CM, et al. Genetic etiology of renal agenesis: fine mapping of Renag1 and identification of kit as the candidate functional gene. PLoS One. 2015;10(2):e0118147.
Arab S, Miyazaki A, Hoang Trung H, Yokoe M, Nakagawa Y, Kaneko T, et al. Long terminal repeat insertion in Kit causes unilateral renal agenesis in rats. Transl Regul Sci. 2020;2(1):30–5.
Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hortnagel K, Pelz HJ, et al. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature. 2004;427(6974):537–41.
Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW. Identification of the gene for vitamin K epoxide reductase. Nature. 2004;427(6974):541–4.
Sasaki N, Hayashizaki Y, Muramatsu M, Matsuda Y, Ando Y, Kuramoto T, et al. The gene responsible for LEC hepatitis, located on rat chromosome 16, is the homolog to the human Wilson disease gene. Biochem Biophys Res Commun. 1994;202(1):512–8.
Wu J, Forbes JR, Chen HS, Cox DW. The LEC rat has a deletion in the copper transporting ATPase gene homologous to the Wilson disease gene. Nat Genet. 1994;7(4):541–5.
Plaas M, Seppa K, Reimets R, Jagomae T, Toots M, Koppel T, et al. Wfs1- deficient rats develop primary symptoms of Wolfram syndrome: insulin-dependent diabetes, optic nerve atrophy and medullary degeneration. Sci Rep. 2017;7(1):10220.
Toots M, Seppa K, Jagomae T, Koppel T, Pallase M, Heinla I, et al. Preventive treatment with liraglutide protects against development of glucose intolerance in a rat model of Wolfram syndrome. Sci Rep. 2018;8(1):10183.
Nakagawa H, Matsubara S, Kuriyama M, Yoshidome H, Fujiyama J, Yoshida H, et al. Cloning of rat lysosomal acid lipase cDNA and identification of the mutation in the rat model of Wolman’s disease. J Lipid Res. 1995;36(10):2212–8.
Spence JP, Reiter JL, Qiu B, Gu H, Garcia DK, Zhang L, et al. Estrogen-dependent upregulation of Adcyap1r1 expression in nucleus Accumbens is associated with genetic predisposition of sex-specific QTL for alcohol consumption on rat chromosome 4. Front Genet. 2018;9:513.
Zhou Z, Karlsson C, Liang T, Xiong W, Kimura M, Tapocik JD, et al. Loss of metabotropic glutamate receptor 2 escalates alcohol consumption. Proc Natl Acad Sci U S A. 2013;110(42):16963–8.
Wood CM, Nicolas CS, Choi SL, Roman E, Nylander I, Fernandez-Teruel A, et al. Prevalence and influence of cys407* Grm2 mutation in Hannover-derived Wistar rats: mGlu2 receptor loss links to alcohol intake, risk taking and emotional behaviour. Neuropharmacology. 2017;115:128–38.
Ding ZM, Ingraham CM, Hauser SR, Lasek AW, Bell RL, McBride WJ. Reduced levels of mGlu2 receptors within the Prelimbic cortex are not associated with elevated glutamate transmission or high alcohol drinking. Alcohol Clin Exp Res. 2017;41(11):1896–906.
Yong W, Spence JP, Eskay R, Fitz SD, Damadzic R, Lai D, et al. Alcohol-preferring rats show decreased corticotropin-releasing hormone-2 receptor expression and differences in HPA activation compared to alcohol-nonpreferring rats. Alcohol Clin Exp Res. 2014;38(5):1275–83.
Lo CL, Lossie AC, Liang T, Liu Y, Xuei X, Lumeng L, et al. High resolution genomic scans reveal genetic architecture controlling alcohol preference in bidirectionally selected rat model. PLoS Genet. 2016;12(8):e1006178.
Qiu B, Bell RL, Cao Y, Zhang L, Stewart RB, Graves T, et al. Npy deletion in an alcohol non-preferring rat model elicits differential effects on alcohol consumption and body weight. J Genet Genomics. 2016;43(7):421–30.
Izumi R, Kusakabe T, Noguchi M, Iwakura H, Tanaka T, Miyazawa T, et al. CRISPR/Cas9-mediated Angptl8 knockout suppresses plasma triglyceride concentrations and adiposity in rats. J Lipid Res. 2018;59(9):1575–85.
Zhou LB, Zheng YM, Liao WJ, Song LJ, Meng X, Gong X, et al. MUC1 deficiency promotes nasal epithelial barrier dysfunction in subjects with allergic rhinitis. J Allergy Clin Immunol. 2019;144(6):1716–9.e5.
Exner EC, Geurts AM, Hoffmann BR, Casati M, Stodola T, Dsouza NR, et al. Interaction between Mas1 and AT1RA contributes to enhancement of skeletal muscle angiogenesis by angiotensin-(1-7) in Dahl salt-sensitive rats. PLoS One. 2020;15(4):e0232067.
Wang M, Sips P, Khin E, Rotival M, Sun X, Ahmed R, et al. Wars2 is a determinant of angiogenesis. Nat Commun. 2016;7:12061.
Falak S, Schafer S, Baud A, Hummel O, Schulz H, Gauguier D, et al. Protease inhibitor 15, a candidate gene for abdominal aortic internal elastic lamina ruptures in the rat. Physiol Genomics. 2014;46(12):418–28.
Swanberg M, Lidman O, Padyukov L, Eriksson P, Akesson E, Jagodic M, et al. MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction. Nat Genet. 2005;37(5):486–94.
Lorentzen JC, Flornes L, Eklow C, Backdahl L, Ribbhammar U, Guo JP, et al. Association of arthritis with a gene complex encoding C-type lectin-like receptors. Arthritis Rheum. 2007;56(8):2620–32.
Rintisch C, Kelkka T, Norin U, Lorentzen JC, Olofsson P, Holmdahl R. Finemapping of the arthritis QTL Pia7 reveals co-localization with Oia2 and the APLEC locus. Genes Immun. 2010;11(3):239–45.
Backdahl L, Ekman D, Jagodic M, Olsson T, Holmdahl R. Identification of candidate risk gene variations by whole-genome sequence analysis of four rat strains commonly used in inflammation research. BMC Genomics. 2014;15:391.
Backdahl L, Aoun M, Norin U, Holmdahl R. Identification of Clec4b as a novel regulator of bystander activation of auto-reactive T cells and autoimmune disease. PLoS Genet. 2020;16(6):e1008788.
Liu F, Shen X, Su S, Cui H, Fang Y, Wang T, et al. FcgammaRI-coupled signaling in peripheral nociceptors mediates joint pain in a rat model of rheumatoid arthritis. Arthritis Rheumatol. 2020; https://doi.org/10.1002/art.41386.
Li H, Guan SB, Lu Y, Wang F, Liu YH, Liu QY. Genetic deletion of GIT2 prolongs functional recovery and suppresses chondrocyte differentiation in rats with rheumatoid arthritis. J Cell Biochem. 2018;119(2):1538–47.
Li H, Jiang W, Ye S, Zhou M, Liu C, Yang X, et al. P2Y14 receptor has a critical role in acute gouty arthritis by regulating pyroptosis of macrophages. Cell Death Dis. 2020;11(5):394.
Laragione T, Brenner M, Lahiri A, Gao E, Harris C, Gulko PS. Huntingtin-interacting protein 1 (HIP1) regulates arthritis severity and synovial fibroblast invasiveness by altering PDGFR and Rac1 signalling. Ann Rheum Dis. 2018;77(11):1627–35.
Hultqvist M, Sareila O, Vilhardt F, Norin U, Olsson LM, Olofsson P, et al. Positioning of a polymorphic quantitative trait nucleotide in the Ncf1 gene controlling oxidative burst response and arthritis severity in rats. Antioxid Redox Signal. 2011;14(12):2373–83.
Olofsson P, Holmberg J, Tordsson J, Lu S, Akerstrom B, Holmdahl R. Positional identification of Ncf1 as a gene that regulates arthritis severity in rats. Nat Genet. 2003;33(1):25–32.
Yau AC, Tuncel J, Haag S, Norin U, Houtman M, Padyukov L, et al. Conserved 33-kb haplotype in the MHC class III region regulates chronic arthritis. Proc Natl Acad Sci U S A. 2016;113(26):E3716–24.
Yau ACY, Tuncel J, Holmdahl R. The major histocompatibility complex class III haplotype Ltab-Ncr3 regulates adjuvant-induced but not antigen-induced autoimmunity. Am J Pathol. 2017;187(5):987–98.
Haag S, Tuncel J, Thordardottir S, Mason DE, Yau AC, Dobritzsch D, et al. Positional identification of RT1-B (HLA-DQ) as susceptibility locus for autoimmune arthritis. J Immunol. 2015;194(6):2539–50.
Guerreiro-Cacais AO, Norin U, Gyllenberg A, Berglund R, Beyeen AD, Rheumatoid Arthritis Consortium I, et al. VAV1 regulates experimental autoimmune arthritis and is associated with anti-CCP negative rheumatoid arthritis. Genes Immun. 2017;18(1):48–56.
Reese RM, Dourado M, Anderson K, Warming S, Stark KL, Balestrini A, et al. Behavioral characterization of a CRISPR-generated TRPA1 knockout rat in models of pain, itch, and asthma. Sci Rep. 2020;10(1):979.
Xu Y, Zhao XM, Liu J, Wang YY, Xiong LL, He XY, et al. Complexin I knockout rats exhibit a complex neurobehavioral phenotype including profound ataxia and marked deficits in lifespan. Pflugers Arch. 2020;472(1):117–33.
Serikawa T, Kunisawa N, Shimizu S, Kato M, Alves Iha H, Kinboshi M, et al. Increased seizure sensitivity, emotional defects and cognitive impairment in PHD finger protein 24 (Phf24)-null rats. Behav Brain Res. 2019;369:111922.
Regan SL, Hufgard JR, Pitzer EM, Sugimoto C, Hu YC, Williams MT, et al. Knockout of latrophilin-3 in Sprague-Dawley rats causes hyperactivity, hyper-reactivity, under-response to amphetamine, and disrupted dopamine markers. Neurobiol Dis. 2019;130:104494.
Regan SL, Cryan MT, Williams MT, Vorhees CV, Ross AE. Enhanced transient striatal dopamine release and reuptake in Lphn3 knockout rats. ACS Chem Neurosci. 2020;11(8):1171–7.
Peeters DGA, de Boer SF, Terneusen A, Newman-Tancredi A, Varney MA, Verkes RJ, et al. Enhanced aggressive phenotype of Tph2 knockout rats is associated with diminished 5-HT1A receptor sensitivity. Neuropharmacology. 2019;153:134–41.
Schroeder M, Weller A. Anxiety-like behavior and locomotion in CCK1 knockout rats as a function of strain, sex and early maternal environment. Behav Brain Res. 2010;211(2):198–207.
Nivard MG, Mbarek H, Hottenga JJ, Smit JH, Jansen R, Penninx BW, et al. Further confirmation of the association between anxiety and CTNND2: replication in humans. Genes Brain Behav. 2014;13(2):195–201.
Baud A, Flint J, Fernadez-Teruel A, TRGSM C. Identification of genetic variants underlying anxiety and multiple sclerosis in heterogeneous stock rats. World J Neurosci. 2014;4:216–24.
Olivier JD, Van Der Hart MG, Van Swelm RP, Dederen PJ, Homberg JR, Cremers T, et al. A study in male and female 5-HT transporter knockout rats: an animal model for anxiety and depression disorders. Neuroscience. 2008;152(3):573–84.
van der Doelen RHA, Robroch B, Arnoldussen IA, Schulpen M, Homberg JR, Kozicz T. Serotonin and urocortin 1 in the dorsal raphe and Edinger-Westphal nuclei after early life stress in serotonin transporter knockout rats. Neuroscience. 2017;340:345–58.
Rutten K, De Vry J, Bruckmann W, Tzschentke TM. Pharmacological blockade or genetic knockout of the NOP receptor potentiates the rewarding effect of morphine in rats. Drug Alcohol Depend. 2011;114(2–3):253–6.
Rizzi A, Molinari S, Marti M, Marzola G, Calo G. Nociceptin/orphanin FQ receptor knockout rats: in vitro and in vivo studies. Neuropharmacology. 2011;60(4):572–9.
Esclassan F, Francois J, Phillips KG, Loomis S, Gilmour G. Phenotypic characterization of nonsocial behavioral impairment in neurexin 1alpha knockout rats. Behav Neurosci. 2015;129(1):74–85.
Homberg JR, Olivier JD, VandenBroeke M, Youn J, Ellenbroek AK, Karel P, et al. The role of the dopamine D1 receptor in social cognition: studies using a novel genetic rat model. Dis Model Mech. 2016;9(10):1147–58.
Leo D, Sukhanov I, Gainetdinov RR. Novel translational rat models of dopamine transporter deficiency. Neural Regen Res. 2018;13(12):2091–3.
Vengeliene V, Bespalov A, Rossmanith M, Horschitz S, Berger S, Relo AL, et al. Towards trans-diagnostic mechanisms in psychiatry: neurobehavioral profile of rats with a loss-of-function point mutation in the dopamine transporter gene. Dis Model Mech. 2017;10(4):451–61.
Rasmus KC, O’Neill CE, Bachtell RK, Cooper DC. Cocaine self-administration in rats lacking a functional trpc4 gene. F1000Res. 2013;2:110.
Sun H, Fu S, Cui S, Yin X, Sun X, Qi X, et al. Development of a CRISPR-SaCas9 system for projection- and function-specific gene editing in the rat brain. Sci Adv. 2020;6(12):eaay6687.
Ma L, Chen X, Zhao B, Shi Y, Han F. Enhanced apoptosis and decreased AMPA receptors are involved in deficit in fear memory in Rin1 knockout rats. J Affect Disord. 2020; in press.
Scheimann JR, Moloney RD, Mahbod P, Morano RL, Fitzgerald M, Hoskins O, et al. Conditional deletion of glucocorticoid receptors in rat brain results in sex-specific deficits in fear and coping behaviors. Elife. 2019;8:e44672.
Barnett BR, Torres-Velazquez M, Yi SY, Rowley PA, Sawin EA, Rubinstein CD, et al. Sex-specific deficits in neurite density and white matter integrity are associated with targeted disruption of exon 2 of the Disc1 gene in the rat. Transl Psychiatry. 2019;9(1):82.
Kisko TM, Braun MD, Michels S, Witt SH, Rietschel M, Culmsee C, et al. Cacna1c haploinsufficiency leads to pro-social 50-kHz ultrasonic communication deficits in rats. Dis Model Mech. 2018;11(6):dmm034116.
Braun MD, Kisko TM, Vecchia DD, Andreatini R, Schwarting RKW, Wohr M. Sex-specific effects of Cacna1c haploinsufficiency on object recognition, spatial memory, and reversal learning capabilities in rats. Neurobiol Learn Mem. 2018;155:543–55.
Ackermann F, Schink KO, Bruns C, Izsvak Z, Hamra FK, Rosenmund C, et al. Critical role for Piccolo in synaptic vesicle retrieval. Elife. 2019;8:e46629.
Falck J, Bruns C, Hoffmann-Conaway S, Straub I, Plautz EJ, Orlando M, et al. Loss of piccolo function in rats induces cerebellar network dysfunction and pontocerebellar hypoplasia type 3-like phenotypes. J Neurosci. 2020;40(14):2943–59.
Golub Y, Schildbach EM, Touma C, Kratz O, Moll GH, von Horsten S, et al. Role of hypothalamus-pituitary-adrenal axis modulation in the stress-resilient phenotype of DPP4-deficient rats. Behav Brain Res. 2019;356:243–9.
Jeanneteau F, Barrere C, Vos M, De Vries CJM, Rouillard C, Levesque D, et al. The stress-induced transcription factor NR4A1 adjusts mitochondrial function and synapse number in prefrontal cortex. J Neurosci. 2018;38(6):1335–50.
Taylor SB, Taylor AR, Markham JA, Geurts AM, Kanaskie BZ, Koenig JI. Disruption of the neuregulin 1 gene in the rat alters HPA axis activity and behavioral responses to environmental stimuli. Physiol Behav. 2011;104(2):205–14.
Ferdaus MZ, Xiao B, Ohara H, Nemoto K, Harada Y, Saar K, et al. Identification of Stim1 as a candidate gene for exaggerated sympathetic response to stress in the stroke-prone spontaneously hypertensive rat. PLoS One. 2014;9(4):e95091.
Ohara H, Nabika T. A nonsense mutation of Stim1 identified in stroke-prone spontaneously hypertensive rats decreased the store-operated calcium entry in astrocytes. Biochem Biophys Res Commun. 2016;476(4):406–11.
Deruyver Y, Weyne E, Dewulf K, Rietjens R, Pinto S, Van Ranst N, et al. Intravesical activation of the Cation Channel TRPV4 improves bladder function in a rat model for detrusor underactivity. Eur Urol. 2018;74(3):336–45.
Gopalakrishnan K, Kumarasamy S, Abdul-Majeed S, Kalinoski AL, Morgan EE, Gohara AF, et al. Targeted disruption of Adamts16 gene in a rat genetic model of hypertension. Proc Natl Acad Sci U S A. 2012;109(50):20555–9.
Joe B, Saad Y, Dhindaw S, Lee NH, Frank BC, Achinike OH, et al. Positional identification of variants of Adamts16 linked to inherited hypertension. Hum Mol Genet. 2009;18(15):2825–38.
Citterio L, Lanzani C, Manunta P, Bianchi G. Genetics of primary hypertension: the clinical impact of adducin polymorphisms. Biochim Biophys Acta. 2010;1802(12):1285–98.
Tripodi G, Florio M, Ferrandi M, Modica R, Zimdahl H, Hubner N, et al. Effect of Add1 gene transfer on blood pressure in reciprocal congenic strains of Milan rats. Biochem Biophys Res Commun. 2004;324(2):562–8.
Woon PY, Kaisaki PJ, Braganca J, Bihoreau MT, Levy JC, Farrall M, et al. Aryl hydrocarbon receptor nuclear translocator-like (BMAL1) is associated with susceptibility to hypertension and type 2 diabetes. Proc Natl Acad Sci U S A. 2007;104(36):14412–7.
Rudemiller N, Lund H, Jacob HJ, Geurts AM, Mattson DL, PhysGen Knockout P. CD247 modulates blood pressure by altering T-lymphocyte infiltration in the kidney. Hypertension. 2014;63(3):559–64.
Ehret GB, O’Connor AA, Weder A, Cooper RS, Chakravarti A. Follow-up of a major linkage peak on chromosome 1 reveals suggestive QTLs associated with essential hypertension: GenNet study. Eur J Hum Genet. 2009;17(12):1650–7.
Deng AY, deBlois D, Laporte SA, Gelinas D, Tardif JC, Thorin E, et al. Novel pathogenesis of hypertension and diastolic dysfunction caused by M3R (muscarinic cholinergic 3 receptor) signaling. Hypertension. 2018;72(3):755–64.
Prisco SZ, Prokop JW, Sarkis AB, Yeo NC, Hoffman MJ, Hansen CC, et al. Refined mapping of a hypertension susceptibility locus on rat chromosome 12. Hypertension. 2014;64(4):883–90.
Garrett MR, Rapp JP. Defining the blood pressure QTL on chromosome 7 in Dahl rats by a 177-kb congenic segment containing Cyp11b1. Mamm Genome. 2003;14(4):268–73.
Low TY, van Heesch S, van den Toorn H, Giansanti P, Cristobal A, Toonen P, et al. Quantitative and qualitative proteome characteristics extracted from in-depth integrated genomics and proteomics analysis. Cell Rep. 2013;5(5):1469–78.
Seda O, Liska F, Pravenec M, Vernerova Z, Kazdova L, Krenova D, et al. Connexin 50 mutation lowers blood pressure in spontaneously hypertensive rat. Physiol Res. 2017;66(1):15–28.
Waghulde H, Cheng X, Galla S, Mell B, Cai J, Pruett-Miller SM, et al. Attenuation of microbiotal dysbiosis and hypertension in a CRISPR/Cas9 gene ablation rat model of GPER1. Hypertension. 2018;72(5):1125–32.
Mullins LJ, Kenyon CJ, Bailey MA, Conway BR, Diaz ME, Mullins JJ. Mineralocorticoid excess or glucocorticoid insufficiency: renal and metabolic phenotypes in a Rat Hsd11b2 knockout model. Hypertension. 2015;66(3):667–73.
Seitz BM, Demireva EY, Xie H, Fink GD, Krieger-Burke T, Burke WM, et al. 5-HT does not lower blood pressure in the 5-HT7 knockout rat. Physiol Genomics. 2019;51(7):302–10.
Zhou X, Zhang Z, Shin MK, Horwitz SB, Levorse JM, Zhu L, et al. Heterozygous disruption of renal outer medullary potassium channel in rats is associated with reduced blood pressure. Hypertension. 2013;62(2):288–94.
Palygin O, Levchenko V, Ilatovskaya DV, Pavlov TS, Pochynyuk OM, Jacob HJ, et al. Essential role of Kir5.1 channels in renal salt handling and blood pressure control. JCI Insight. 2017;2(18):e92331.