Mammalian Genome

, 22:466 | Cite as

The emerging role for rat models in gene discovery

  • Melinda R. Dwinell
  • Jozef Lazar
  • Aron M. Geurts


Rat models have been used for many decades to study physiological and pathophysiological mechanisms. Prior to the release of the rat genome and new technologies for targeting gene manipulation, the rat had been the underdog in the genomics era, despite the abundance of physiological data compared to the mouse. The overarching goal of biomedical research is to improve health and advance medical science. Translating human disease gene discovery and validation in the rat, through the use of emerging technologies and integrated tools and databases, is providing power to understand the genetics, environmental influences, and biology of disease. In this review we briefly outline the rat models, bioinformatics tools, and technologies that are changing the landscape of translational research. The strategies used to translate disease traits to genes to function, and, ultimately, to improve human health is discussed. Finally, our perspective on how rat models will continue to positively impact biomedical research is provided.



This work was supported in part by NIH NHLBI grants 5RC2HL101681 and 5R01HL064541. We thank the Rat Genome Database curation and programming staff (Rajni Nigam, Marek Tutaj, Pushkala Jayaraman) for the preparation of data and figures used within this article.


  1. Abbott A (2009) Return of the rat. Nature 460:788PubMedCrossRefGoogle Scholar
  2. Abbott A (2010) Neuroscience: the rat pack. Nature 465:282–283PubMedCrossRefGoogle Scholar
  3. Adamovic T, McAllister D, Rowe JJ, Wang T, Jacob HJ, Sugg SL (2008) Genetic mapping of mammary tumor traits to rat chromosome 10 using a novel panel of consomic rats. Cancer Genet Cytogenet 186:41–48PubMedCrossRefGoogle Scholar
  4. Adamovic T, McAllister D, Wang T, Adamovic D, Rowe JJ, Moreno C, Lazar J, Jacob HJ, Sugg SL (2010) Identification of novel carcinogen-mediated mammary tumor susceptibility loci in the rat using the chromosome substitution technique. Genes Chromosomes Cancer 49:1035–1045PubMedCrossRefGoogle Scholar
  5. Aitman TJ, Critser JK, Cuppen E, Dominiczak A, Fernandez-Suarez XM, Flint J, Gauguier D, Geurts AM, Gould M, Harris PC, Holmdahl R, Hubner N, Izsvak Z, Jacob HJ, Kuramoto T, Kwitek AE, Marrone A, Mashimo T, Moreno C, Mullins J, Mullins L, Olsson T, Pravenec M, Riley L, Saar K, Serikawa T, Shull JD, Szpirer C, Twigger SN, Voigt B, Worley K (2008) Progress and prospects in rat genetics: a community view. Nat Genet 40:516–522PubMedCrossRefGoogle Scholar
  6. Alam I, Koller DL, Sun Q, Roeder RK, Canete T, Blazquez G, Lopez-Aumatell R, Martinez-Membrives E, Vicens-Costa E, Mont C, Diaz S, Tobena A, Fernandez-Teruel A, Whitley A, Strid P, Diez M, Johannesson M, Flint J, Econs MJ, Turner CH, Foroud T (2011) Heterogeneous stock rat: a unique animal model for mapping genes influencing bone fragility. Bone 48(5):1169–1177PubMedCrossRefGoogle Scholar
  7. Bice PJ, Liang T, Zhang L, Graves TJ, Carr LG, Lai D, Kimpel MW, Foroud T (2010) Fine mapping and expression of candidate genes within the chromosome 10 QTL region of the high and low alcohol-drinking rats. Alcohol 44:477–485PubMedCrossRefGoogle Scholar
  8. Bonnet S, Michelakis ED, Porter CJ, Andrade-Navarro MA, Thebaud B, Haromy A, Harry G, Moudgil R, McMurtry MS, Weir EK, Archer SL (2006) An abnormal mitochondrial-hypoxia inducible factor-1alpha-Kv channel pathway disrupts oxygen sensing and triggers pulmonary arterial hypertension in fawn hooded rats: similarities to human pulmonary arterial hypertension. Circulation 113:2630–2641PubMedCrossRefGoogle Scholar
  9. Buehr M, Meek S, Blair K, Yang J, Ure J, Silva J, McLay R, Hall J, Ying QL, Smith A (2008) Capture of authentic embryonic stem cells from rat blastocysts. Cell 135:1287–1298PubMedCrossRefGoogle Scholar
  10. Chang MY, Kim D, Kim CH, Kang HC, Yang E, Moon JI, Ko S, Park J, Park KS, Lee KA, Hwang DY, Chung Y, Lanza R, Kim KS (2010) Direct reprogramming of rat neural precursor cells and fibroblasts into pluripotent stem cells. PLoS One 5:e9838PubMedCrossRefGoogle Scholar
  11. Cowley AW Jr, Roman RJ, Kaldunski ML, Dumas P, Dickhout JG, Greene AS, Jacob HJ (2001) Brown Norway chromosome 13 confers protection from high salt to consomic Dahl S rat. Hypertension 37:456–461PubMedGoogle Scholar
  12. Cowley AW Jr, Liang M, Roman RJ, Greene AS, Jacob HJ (2004) Consomic rat model systems for physiological genomics. Acta Physiol Scand 181:585–592PubMedCrossRefGoogle Scholar
  13. Cui X, Ji D, Fisher DA, Wu Y, Briner DM, Weinstein EJ (2011) Targeted integration in rat and mouse embryos with zinc-finger nucleases. Nat Biotechnol 29:64–67PubMedCrossRefGoogle Scholar
  14. Dwinell MR, Forster HV, Petersen J, Rider A, Kunert MP, Cowley AW Jr, Jacob HJ (2005) Genetic determinants on rat chromosome 6 modulate variation in the hypercapnic ventilatory response using consomic strains. J Appl Physiol 98:1630–1638PubMedCrossRefGoogle Scholar
  15. Dwinell MR, Worthey EA, Shimoyama M, Bakir-Gungor B, DePons J, Laulederkind S, Lowry T, Nigram R, Petri V, Smith J, Stoddard A, Twigger SN, Jacob HJ (2009) The Rat Genome Database 2009: variation, ontologies and pathways. Nucleic Acids Res 37:D744–D749PubMedCrossRefGoogle Scholar
  16. Ferrandi M, Molinari I, Torielli L, Padoani G, Salardi S, Rastaldi MP, Ferrari P, Bianchi G (2010) Adducin- and ouabain-related gene variants predict the antihypertensive activity of rostafuroxin, part 1: experimental studies. Sci Transl Med 2:59ra86PubMedGoogle Scholar
  17. Geurts AM, Moreno C (2010) Zinc-finger nucleases: new strategies to target the rat genome. Clin Sci (Lond) 119:303–311CrossRefGoogle Scholar
  18. Geurts AM, Cost GJ, Freyvert Y, Zeitler B, Miller JC, Choi VM, Jenkins SS, Wood A, Cui X, Meng X, Vincent A, Lam S, Michalkiewicz M, Schilling R, Foeckler J, Kalloway S, Weiler H, Menoret S, Anegon I, Davis GD, Zhang L, Rebar EJ, Gregory PD, Urnov FD, Jacob HJ, Buelow R (2009) Knockout rats via embryo microinjection of zinc-finger nucleases. Science 325:433PubMedCrossRefGoogle Scholar
  19. Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer S, Scott G, Steffen D, Worley KC, Burch PE, Okwuonu G, Hines S, Lewis L, DeRamo C, Delgado O, Dugan-Rocha S, Miner G, Morgan M, Hawes A, Gill R, Celera, Holt RA, Adams MD, Amanatides PG, Baden-Tillson H, Barnstead M, Chin S, Evans CA, Ferriera S, Fosler C, Glodek A, Gu Z, Jennings D, Kraft CL, Nguyen T, Pfannkoch CM, Sitter C, Sutton GG, Venter JC, Woodage T, Smith D, Lee HM, Gustafson E, Cahill P, Kana A, Doucette-Stamm L, Weinstock K, Fechtel K, Weiss RB, Dunn DM, Green ED, Blakesley RW, Bouffard GG, De Jong PJ, Osoegawa K, Zhu B, Marra M, Schein J, Bosdet I, Fjell C, Jones S, Krzywinski M, Mathewson C, Siddiqui A, Wye N, McPherson J, Zhao S, Fraser CM, Shetty J, Shatsman S, Geer K, Chen Y, Abramzon S, Nierman WC, Havlak PH, Chen R, Durbin KJ, Egan A, Ren Y, Song XZ, Li B, Liu Y, Qin X, Cawley S, Cooney AJ, D’Souza LM, Martin K, Wu JQ, Gonzalez-Garay ML, Jackson AR, Kalafus KJ, McLeod MP, Milosavljevic A, Virk D, Volkov A, Wheeler DA, Zhang Z, Bailey JA, Eichler EE, Tuzun E, Birney E, Mongin E, Ureta-Vidal A, Woodwark C, Zdobnov E, Bork P, Suyama M, Torrents D, Alexandersson M, Trask BJ, Young JM, Huang H, Wang H, Xing H, Daniels S, Gietzen D, Schmidt J, Stevens K, Vitt U, Wingrove J, Camara F, Mar Alba M, Abril JF, Guigo R, Smit A, Dubchak I, Rubin EM, Couronne O, Poliakov A, Hubner N, Ganten D, Goesele C, Hummel O, Kreitler T, Lee YA, Monti J, Schulz H, Zimdahl H, Himmelbauer H, Lehrach H, Jacob HJ, Bromberg S, Gullings-Handley J, Jensen-Seaman MI, Kwitek AE, Lazar J, Pasko D, Tonellato PJ, Twigger S, Ponting CP, Duarte JM, Rice S, Goodstadt L, Beatson SA, Emes RD, Winter EE, Webber C, Brandt P, Nyakatura G, Adetobi M, Chiaromonte F, Elnitski L, Eswara P, Hardison RC, Hou M, Kolbe D, Makova K, Miller W, Nekrutenko A, Riemer C, Schwartz S, Taylor J, Yang S, Zhang Y, Lindpaintner K, Andrews TD, Caccamo M, Clamp M, Clarke L, Curwen V, Durbin R, Eyras E, Searle SM, Cooper GM, Batzoglou S, Brudno M, Sidow A, Stone EA, Payseur BA, Bourque G, Lopez-Otin C, Puente XS, Chakrabarti K, Chatterji S, Dewey C, Pachter L, Bray N, Yap VB, Caspi A, Tesler G, Pevzner PA, Haussler D, Roskin KM, Baertsch R, Clawson H, Furey TS, Hinrichs AS, Karolchik D, Kent WJ, Rosenbloom KR, Trumbower H, Weirauch M, Cooper DN, Stenson PD, Ma B, Brent M, Arumugam M, Shteynberg D, Copley RR, Taylor MS, Riethman H, Mudunuri U, Peterson J, Guyer M, Felsenfeld A, Old S, Mockrin S, Collins F (2004) Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature 428:493–521PubMedCrossRefGoogle Scholar
  20. Gilibert S, Kwitek AE, Hubner N, Tschannen M, Jacob HJ, Sassard J, Bataillard A (2008) Effects of chromosome 17 on features of the metabolic syndrome in the Lyon hypertensive rat. Physiol Genomics 33:212–217PubMedCrossRefGoogle Scholar
  21. Heinig M, Petretto E, Wallace C, Bottolo L, Rotival M, Lu H, Li Y, Sarwar R, Langley SR, Bauerfeind A, Hummel O, Lee YA, Paskas S, Rintisch C, Saar K, Cooper J, Buchan R, Gray EE, Cyster JG, Erdmann J, Hengstenberg C, Maouche S, Ouwehand WH, Rice CM, Samani NJ, Schunkert H, Goodall AH, Schulz H, Roider HG, Vingron M, Blankenberg S, Munzel T, Zeller T, Szymczak S, Ziegler A, Tiret L, Smyth DJ, Pravenec M, Aitman TJ, Cambien F, Clayton D, Todd JA, Hubner N, Cook SA (2010) A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk. Nature 467:460–464PubMedCrossRefGoogle Scholar
  22. Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, Collins FS, Manolio TA (2009) Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci USA 106:9362–9367PubMedCrossRefGoogle Scholar
  23. Hindorff LA, Junkins HA, Hall PN, Mehta JP, Manolio TA (2011) A catalog of published genome-wide association studies. Available at: Accessed 28 Feb 2011
  24. Huang G, Tong C, Kumbhani DS, Ashton C, Yan H, Ying QL (2011) Beyond knockout rats: new insights into finer genome manipulation in rats. Cell Cycle 10(7):1059–1066PubMedCrossRefGoogle Scholar
  25. Jacob HJ (2010) The rat: a model used in biomedical research. Methods Mol Biol 597:1–11PubMedCrossRefGoogle Scholar
  26. Jacob HJ, Lazar J, Dwinell MR, Moreno C, Geurts AM (2010) Gene targeting in the rat: advances and opportunities. Trends Genet 26:510–518PubMedCrossRefGoogle Scholar
  27. Joe B, Saad Y, Lee NH, Frank BC, Achinike OH, Luu TV, Gopalakrishnan K, Toland EJ, Farms P, Yerga-Woolwine S, Manickavasagam E, Rapp JP, Garrett MR, Coe D, Apte SS, Rankinen T, Perusse L, Ehret GB, Ganesh SK, Cooper RS, O’Connor A, Rice T, Weder AB, Chakravarti A, Rao DC, Bouchard C (2009) Positional identification of variants of Adamts16 linked to inherited hypertension. Hum Mol Genet 18:2825–2838PubMedCrossRefGoogle Scholar
  28. Johannesson M, Lopez-Aumatell R, Stridh P, Diez M, Tuncel J, Blazquez G, Martinez-Membrives E, Canete T, Vicens-Costa E, Graham D, Copley RR, Hernandez-Pliego P, Beyeen AD, Ockinger J, Fernandez-Santamaria C, Gulko PS, Brenner M, Tobena A, Guitart-Masip M, Gimenez-Llort L, Dominiczak A, Holmdahl R, Gauguier D, Olsson T, Mott R, Valdar W, Redei EE, Fernandez-Teruel A, Flint J (2009) A resource for the simultaneous high-resolution mapping of multiple quantitative trait loci in rats: the NIH heterogeneous stock. Genome Res 19:150–158PubMedCrossRefGoogle Scholar
  29. Kawamata M, Ochiya T (2010) Generation of genetically modified rats from embryonic stem cells. Proc Natl Acad Sci USA 107:14223–14228PubMedCrossRefGoogle Scholar
  30. Kunert MP, Drenjancevic-Peric I, Dwinell MR, Lombard JH, Cowley AW Jr, Greene AS, Kwitek AE, Jacob HJ (2006) Consomic strategies to localize genomic regions related to vascular reactivity in the Dahl salt-sensitive rat. Physiol Genomics 26:218–225PubMedCrossRefGoogle Scholar
  31. Kunert MP, Dwinell MR, Lombard JH (2010) Vascular responses in aortic rings of a consomic rat panel derived from the Fawn Hooded Hypertensive strain. Physiol Genomics 42A:244–258PubMedCrossRefGoogle Scholar
  32. Lanzani C, Citterio L, Glorioso N, Manunta P, Tripodi G, Salvi E, Carpini SD, Ferrandi M, Messaggio E, Staessen JA, Cusi D, Macciardi F, Argiolas G, Valentini G, Ferrari P, Bianchi G (2010) Adducin- and ouabain-related gene variants predict the antihypertensive activity of rostafuroxin, part 2: clinical studies. Sci Transl Med 2:59ra87PubMedGoogle Scholar
  33. Li P, Tong C, Mehrian-Shai R, Jia L, Wu N, Yan Y, Maxson RE, Schulze EN, Song H, Hsieh CL, Pera MF, Ying QL (2008) Germline competent embryonic stem cells derived from rat blastocysts. Cell 135:1299–1310PubMedCrossRefGoogle Scholar
  34. Li W, Wei W, Zhu S, Zhu J, Shi Y, Lin T, Hao E, Hayek A, Deng H, Ding S (2009) Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors. Cell Stem Cell 4:16–19PubMedCrossRefGoogle Scholar
  35. Liao J, Cui C, Chen S, Ren J, Chen J, Gao Y, Li H, Jia N, Cheng L, Xiao H, Xiao L (2009) Generation of induced pluripotent stem cell lines from adult rat cells. Cell Stem Cell 4:11–15PubMedCrossRefGoogle Scholar
  36. Manolio TA, Brooks LD, Collins FS (2008) A HapMap harvest of insights into the genetics of common disease. J Clin Invest 118:1590–1605PubMedCrossRefGoogle Scholar
  37. Mashimo T, Yanagihara K, Tokuda S, Voigt B, Takizawa A, Nakajima R, Kato M, Hirabayashi M, Kuramoto T, Serikawa T (2008) An ENU-induced mutant archive for gene targeting in rats. Nat Genet 40:514–515PubMedCrossRefGoogle Scholar
  38. Mashimo T, Ohmori I, Ouchida M, Ohno Y, Tsurumi T, Miki T, Wakamori M, Ishihara S, Yoshida T, Takizawa A, Kato M, Hirabayashi M, Sasa M, Mori Y, Serikawa T (2010a) A missense mutation of the gene encoding voltage-dependent sodium channel (Nav1.1) confers susceptibility to febrile seizures in rats. J Neurosci 30:5744–5753PubMedCrossRefGoogle Scholar
  39. Mashimo T, Takizawa A, Voigt B, Yoshimi K, Hiai H, Kuramoto T, Serikawa T (2010b) Generation of knockout rats with X-linked severe combined immunodeficiency (X-SCID) using zinc-finger nucleases. PLoS One 5:e8870PubMedCrossRefGoogle Scholar
  40. Mattson DL, Dwinell MR, Greene AS, Kwitek AE, Roman RJ, Jacob HJ, Cowley AW Jr (2008) Chromosome substitution reveals the genetic basis of Dahl salt-sensitive hypertension and renal disease. Am J Physiol Renal Physiol 295:F837–F842PubMedCrossRefGoogle Scholar
  41. Mayer AN, Dimmock DP, Arca MJ, Bick DP, Verbsky JW, Worthey EA, Jacob HJ, Margolis DA (2011) A timely arrival for genomic medicine. Genet Med 13:195–196PubMedCrossRefGoogle Scholar
  42. Meyer M, de Angelis MH, Wurst W, Kuhn R (2010) Gene targeting by homologous recombination in mouse zygotes mediated by zinc-finger nucleases. Proc Natl Acad Sci USA 107:15022–15026PubMedCrossRefGoogle Scholar
  43. Moreno C, Lazar J, Jacob HJ, Kwitek AE (2008) Comparative genomics for detecting human disease genes. Adv Genet 60:655–697PubMedCrossRefGoogle Scholar
  44. Moreno C, Hoffman M, Stodola TJ, Didier DN, Lazar J, Geurts AM, North PE, Jacob HJ, Greene AS (2011a) Creation and characterization of a renin knockout rat. Hypertension 57:614–619PubMedCrossRefGoogle Scholar
  45. Moreno C, Williams JM, Lu L, Liang M, Lazar J, Jacob HJ, Cowley AW Jr, Roman RJ (2011b) Narrowing a region on rat chromosome 13 that protects against hypertension in Dahl SS-13BN congenic strains. Am J Physiol Heart Circ Physiol 300(4):H1530–H1535PubMedCrossRefGoogle Scholar
  46. Mott R, Talbot CJ, Turri MG, Collins AC, Flint J (2000) A method for fine mapping quantitative trait loci in outbred animal stocks. Proc Natl Acad Sci USA 97:12649–12654PubMedCrossRefGoogle Scholar
  47. Olivier JD, Van Der Hart MG, Van Swelm RP, Dederen PJ, Homberg JR, Cremers T, Deen PM, Cuppen E, Cools AR, Ellenbroek BA (2008) A study in male and female 5-HT transporter knockout rats: an animal model for anxiety and depression disorders. Neuroscience 152:573–584PubMedCrossRefGoogle Scholar
  48. Petretto E, Sarwar R, Grieve I, Lu H, Kumaran MK, Muckett PJ, Mangion J, Schroen B, Benson M, Punjabi PP, Prasad SK, Pennell DJ, Kiesewetter C, Tasheva ES, Corpuz LM, Webb MD, Conrad GW, Kurtz TW, Kren V, Fischer J, Hubner N, Pinto YM, Pravenec M, Aitman TJ, Cook SA (2008) Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass. Nat Genet 40:546–552PubMedCrossRefGoogle Scholar
  49. Pravenec M, Kurtz TW (2010) Recent advances in genetics of the spontaneously hypertensive rat. Curr Hypertens Rep 12:5–9PubMedCrossRefGoogle Scholar
  50. Pravenec M, Klir P, Kren V, Zicha J, Kunes J (1989) An analysis of spontaneous hypertension in spontaneously hypertensive rats by means of new recombinant inbred strains. J Hypertens 7:217–221PubMedCrossRefGoogle Scholar
  51. Pravenec M, Churchill PC, Churchill MC, Viklicky O, Kazdova L, Aitman TJ, Petretto E, Hubner N, Wallace CA, Zimdahl H, Zidek V, Landa V, Dunbar J, Bidani A, Griffin K, Qi N, Maxova M, Kren V, Mlejnek P, Wang J, Kurtz TW (2008a) Identification of renal Cd36 as a determinant of blood pressure and risk for hypertension. Nat Genet 40:952–954PubMedCrossRefGoogle Scholar
  52. Pravenec M, Kazdova L, Landa V, Zidek V, Mlejnek P, Simakova M, Jansa P, Forejt J, Kren V, Krenova D, Qi N, Wang JM, Chan D, Aitman TJ, Kurtz TW (2008b) Identification of mutated Srebf1 as a QTL influencing risk for hepatic steatosis in the spontaneously hypertensive rat. Hypertension 51:148–153PubMedCrossRefGoogle Scholar
  53. Rangel-Filho A, Sharma M, Datta YH, Moreno C, Roman RJ, Iwamoto Y, Provoost AP, Lazar J, Jacob HJ (2005) RF-2 gene modulates proteinuria and albuminuria independently of changes in glomerular permeability in the fawn-hooded hypertensive rat. J Am Soc Nephrol 16:852–856PubMedCrossRefGoogle Scholar
  54. Roman RJ, Cowley AW Jr, Greene A, Kwitek AE, Tonellato PJ, Jacob HJ (2002) Consomic rats for the identification of genes and pathways underlying cardiovascular disease. Cold Spring Harb Symp Quant Biol 67:309–315PubMedCrossRefGoogle Scholar
  55. Schulz A, Schutten S, Schulte L, Kossmehl P, Nyengaard JR, Vetter R, Huber M, Kreutz R (2010) Genetic locus on MWF rat chromosome 6 affects kidney damage in response to L-NAME treatment in spontaneously hypertensive rats. Physiol Genomics 42:126–133PubMedCrossRefGoogle Scholar
  56. Serikawa T, Mashimo T, Takizawa A, Okajima R, Maedomari N, Kumafuji K, Tagami F, Neoda Y, Otsuki M, Nakanishi S, Yamasaki K, Voigt B, Kuramoto T (2009) National BioResource Project—rat and related activities. Exp Anim 58:333–341PubMedCrossRefGoogle Scholar
  57. Shao H, Sinasac DS, Burrage LC, Hodges CA, Supelak PJ, Palmert MR, Moreno C, Cowley AW Jr, Jacob HJ, Nadeau JH (2010) Analyzing complex traits with congenic strains. Mamm Genome 21:276–286PubMedCrossRefGoogle Scholar
  58. Solberg Woods LC, Holl K, Tschannen M, Valdar W (2010a) Fine-mapping a locus for glucose tolerance using heterogeneous stock rats. Physiol Genomics 41:102–108PubMedCrossRefGoogle Scholar
  59. Solberg Woods LC, Stelloh C, Regner KR, Schwabe T, Eisenhauer J, Garrett MR (2010b) Heterogeneous stock rats: a new model to study the genetics of renal phenotypes. Am J Physiol Renal Physiol 298:F1484–F1491PubMedCrossRefGoogle Scholar
  60. Thomas KR, Capecchi MR (1990) Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development. Nature 346:847–850PubMedCrossRefGoogle Scholar
  61. Tong C, Li P, Wu NL, Yan Y, Ying QL (2010) Production of p53 gene knockout rats by homologous recombination in embryonic stem cells. Nature 467:211–213PubMedCrossRefGoogle Scholar
  62. Twigger SN, Pruitt KD, Fernandez-Suarez XM, Karolchik D, Worley KC, Maglott DR, Brown G, Weinstock G, Gibbs RA, Kent J, Birney E, Jacob HJ (2008) What everybody should know about the rat genome and its online resources. Nat Genet 40:523–527PubMedCrossRefGoogle Scholar
  63. van Boxtel R, Toonen PW, Verheul M, van Roekel HS, Nijman IJ, Guryev V, Cuppen E (2008) Improved generation of rat gene knockouts by target-selected mutagenesis in mismatch repair-deficient animals. BMC Genomics 9:460PubMedCrossRefGoogle Scholar
  64. Wang K, Narayanan M, Zhong H, Tompa M, Schadt EE, Zhu J (2009) Meta-analysis of inter-species liver co-expression networks elucidates traits associated with common human diseases. PLoS Comput Biol 5:e1000616PubMedCrossRefGoogle Scholar
  65. Worthey EA, Stoddard AJ, Jacob HJ (2010) Sequencing of the rat genome and databases. Methods Mol Biol 597:33–53PubMedCrossRefGoogle Scholar
  66. Worthey EA, Mayer AN, Syverson GD, Helbling D, Bonacci BB, Decker B, Serpe JM, Dasu T, Tschannen MR, Veith RL, Basehore MJ, Broeckel U, Tomita-Mitchell A, Arca MJ, Casper JT, Margolis DA, Bick DP, Hessner MJ, Routes JM, Verbsky JW, Jacob HJ, Dimmock DP (2011) Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Genet Med 13:255–262PubMedCrossRefGoogle Scholar
  67. Yoshimi K, Tanaka T, Takizawa A, Kato M, Hirabayashi M, Mashimo T, Serikawa T, Kuramoto T (2009) Enhanced colitis-associated colon carcinogenesis in a novel Apc mutant rat. Cancer Sci 100:2022–2027PubMedCrossRefGoogle Scholar
  68. Zan Y, Haag JD, Chen KS, Shepel LA, Wigington D, Wang YR, Hu R, Lopez-Guajardo CC, Brose HL, Porter KI, Leonard RA, Hitt AA, Schommer SL, Elegbede AF, Gould MN (2003) Production of knockout rats using ENU mutagenesis and a yeast-based screening assay. Nat Biotechnol 21:645–651PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Melinda R. Dwinell
    • 1
    • 3
  • Jozef Lazar
    • 2
    • 3
  • Aron M. Geurts
    • 1
    • 3
  1. 1.Department of PhysiologyMedical College of WisconsinMilwaukeeUSA
  2. 2.Department of DermatologyMedical College of WisconsinMilwaukeeUSA
  3. 3.Human and Molecular Genetics CenterMedical College of WisconsinMilwaukeeUSA

Personalised recommendations