Skip to main content

Advertisement

SpringerLink
Log in

Mouse models and type 2 diabetes: translational opportunities

  • Published:
Mammalian Genome Aims and scope Submit manuscript

Abstract

Type 2 diabetes prevalence is increasing worldwide. Treatments are available, but glycaemic control is not always effective in many patients. Better models are needed to create new and improved therapies and to expand our understanding of how type 2 diabetes begins and progresses. Translational research involves the transformation of knowledge from basic scientific discoveries to impacting on public health. This can allow identification of novel molecular mechanisms underlying the disease which can lead to preventative measures, biomarkers for diagnosis, or future therapies. Generation of genetically modified mice has allowed us to investigate the function of genes and develop reproducible models in which the phenotype of the animal can be tested. Mouse models have already given us insight into glucose metabolism and insulin secretion, identified novel pathways, and have been used to confirm genome-wide association studies. In this review we discuss the use of the mouse to clarify human genome-wide association study loci, understand genes and pathways involved in type 2 diabetes, and uncover novel targets for drug discovery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Accili D, Drago J, Lee EJ, Johnson MD, Cool MH, Salvatore P, Asico LD, Jose PA, Taylor SI, Westphal H (1996) Early neonatal death in mice homozygous for a null allele of the insulin receptor gene. Nat Genet 12:106–109

    Article  PubMed  CAS  Google Scholar 

  • Acevedo-Arozena A, Wells S, Potter P, Kelly M, Cox RD, Brown SD (2008) ENU mutagenesis, a way forward to understand gene function. Annu Rev Genomics Hum Genet 9:49–69

    Article  PubMed  CAS  Google Scholar 

  • Almind K, Kahn CR (2004) Genetic determinants of energy expenditure and insulin resistance in diet-induced obesity in mice. Diabetes 53:3274–3285

    Article  PubMed  CAS  Google Scholar 

  • Anastassiadis K, Fu J, Patsch C, Hu S, Weidlich S, Duerschke K, Buchholz F, Edenhofer F, Stewart AF (2009) Dre recombinase, like Cre, is a highly efficient site-specific recombinase in E. coli, mammalian cells and mice. Dis Model Mech 2:508–515

    Article  PubMed  CAS  Google Scholar 

  • Bali D, Svetlanov A, Lee HW, Fusco-Demane D, Leiser M, Li B, Barzilai N, Surana M, Hou H, Fleischer N et al (1995) Animal model for maturity-onset diabetes of the young generated by disruption of the mouse glucokinase gene. J Biol Chem 270:21464–21467

    Article  PubMed  CAS  Google Scholar 

  • Barnett AH, Eff C, Leslie RD, Pyke DA (1981) Diabetes in identical twins. A study of 200 pairs. Diabetologia 20:87–93

    Article  PubMed  CAS  Google Scholar 

  • Bell GI, Xiang KS, Newman MV, Wu SH, Wright LG, Fajans SS, Spielman RS, Cox NJ (1991) Gene for non-insulin-dependent diabetes mellitus (maturity-onset diabetes of the young subtype) is linked to DNA polymorphism on human chromosome 20q. Proc Natl Acad Sci USA 88:1484–1488

    Article  PubMed  CAS  Google Scholar 

  • Biddinger SB, Almind K, Miyazaki M, Kokkotou E, Ntambi JM, Kahn CR (2005) Effects of diet and genetic background on sterol regulatory element-binding protein-1c, stearoyl-CoA desaturase 1, and the development of the metabolic syndrome. Diabetes 54:1314–1323

    Article  PubMed  CAS  Google Scholar 

  • Bluher M, Michael MD, Peroni OD, Ueki K, Carter N, Kahn BB, Kahn CR (2002) Adipose tissue selective insulin receptor knockout protects against obesity and obesity-related glucose intolerance. Dev Cell 3:25–38

    Article  PubMed  CAS  Google Scholar 

  • Bluher M, Kahn BB, Kahn CR (2003) Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299:572–574

    Article  PubMed  Google Scholar 

  • Bluher M, Patti ME, Gesta S, Kahn BB, Kahn CR (2004) Intrinsic heterogeneity in adipose tissue of fat-specific insulin receptor knock-out mice is associated with differences in patterns of gene expression. J Biol Chem 279:31891–31901

    Article  PubMed  Google Scholar 

  • Bogani D, Willoughby C, Davies J, Kaur K, Mirza G, Paudyal A, Haines H, Mckeone R, Cadman M, Pieles G, Schneider JE, Bhattacharya S, Hardy A, Nolan PM, Tripodis N, Depew MJ, Chandrasekara R, Duncan G, Sharpe PT, Greenfield A, Denny P, Brown SD, Ragoussis J, Arkell RM (2005) Dissecting the genetic complexity of human 6p deletion syndromes by using a region-specific, phenotype-driven mouse screen. Proc Natl Acad Sci USA 102:12477–12482

    Article  PubMed  CAS  Google Scholar 

  • Brault V, Besson V, Magnol L, Duchon A, Herault Y (2007) Cre/loxP-mediated chromosome engineering of the mouse genome. Handb Exp Pharmacol (178):29–48

  • Brehm MA, Shultz LD, Greiner DL (2010) Humanized mouse models to study human diseases. Curr Opin Endocrinol Diabetes Obes 17:120–125

    Article  PubMed  Google Scholar 

  • Bruning JC, Michael MD, Winnay JN, Hayashi T, Horsch D, Accili D, Goodyear LJ, Kahn CR (1998) A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol Cell 2:559–569

    Article  PubMed  CAS  Google Scholar 

  • Bruning JC, Gautam D, Burks DJ, Gillette J, Schubert M, Orban PC, Klein R, Krone W, Muller-Wieland D, Kahn CR (2000) Role of brain insulin receptor in control of body weight and reproduction. Science 289:2122–2125

    Article  PubMed  CAS  Google Scholar 

  • Capecchi MR (1989) Altering the genome by homologous recombination. Science 244:1288–1292

    Article  PubMed  CAS  Google Scholar 

  • Church C, Lee S, Bagg EA, Mctaggart JS, Deacon R, Gerken T, Lee A, Moir L, Mecinovic J, Quwailid MM, Schofield CJ, Ashcroft FM, Cox RD (2009) A mouse model for the metabolic effects of the human fat mass and obesity associated FTO gene. PLoS Genet 5:e1000599

    Article  PubMed  Google Scholar 

  • Church C, Moir L, McMurray F, Girard C, Banks GT, Teboul L, Wells S, Bruning JC, Nolan PM, Ashcroft FM, Cox RD (2010) Overexpression of Fto leads to increased food intake and results in obesity. Nat Genet 42(12):1086–1092

    Article  PubMed  CAS  Google Scholar 

  • Coghill EL, Hugill A, Parkinson N, Davison C, Glenister P, Clements S, Hunter J, Cox RD, Brown SD (2002) A gene-driven approach to the identification of ENU mutants in the mouse. Nat Genet 30:255–256

    Article  PubMed  Google Scholar 

  • Collins FS, Rossant J, Wurst W (2007) A mouse for all reasons. Cell 128:9–13

    Article  PubMed  CAS  Google Scholar 

  • Cox RD, Church CD (2011) Mouse models and the interpretation of human GWAS in type 2 diabetes and obesity. Dis Model Mech 4:155–164

    Article  PubMed  CAS  Google Scholar 

  • Dixit R, Boelsterli UA (2007) Healthy animals and animal models of human disease(s) in safety assessment of human pharmaceuticals, including therapeutic antibodies. Drug Discov Today 12:336–342

    Article  PubMed  CAS  Google Scholar 

  • Fajans SS, Bell GI, Polonsky KS (2001) Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young. N Engl J Med 345:971–980

    Article  PubMed  CAS  Google Scholar 

  • Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Bruning JC, Ruther U (2009) Inactivation of the Fto gene protects from obesity. Nature 458:894–898

    Article  PubMed  CAS  Google Scholar 

  • Flint J (2011) Mapping quantitative traits and strategies to find quantitative trait genes. Methods 53:163–174

    Article  PubMed  CAS  Google Scholar 

  • Flint J, Valdar W, Shifman S, Mott R (2005) Strategies for mapping and cloning quantitative trait genes in rodents. Nat Rev Genet 6:271–286

    Article  PubMed  CAS  Google Scholar 

  • Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben-Shlomo Y, Jarvelin MR, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJ, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon LR, Walker M, Hitman GA, Palmer CN, Doney AS, Morris AD, Smith GD, Hattersley AT, McCarthy MI (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316:889–894

    Article  PubMed  CAS  Google Scholar 

  • Froguel P, Vaxillaire M, Sun F, Velho G, Zouali H, Butel MO, Lesage S, Vionnet N, Clement K, Fougerousse F et al (1992) Close linkage of glucokinase locus on chromosome 7p to early-onset non-insulin-dependent diabetes mellitus. Nature 356:162–164

    Article  PubMed  CAS  Google Scholar 

  • 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 325:433

    Article  PubMed  CAS  Google Scholar 

  • Goldsworthy M, Hugill A, Freeman H, Horner E, Shimomura K, Bogani D, Pieles G, Mijat V, Arkell R, Bhattacharya S, Ashcroft FM, Cox RD (2008) Role of the transcription factor sox4 in insulin secretion and impaired glucose tolerance. Diabetes 57:2234–2244

    Article  PubMed  CAS  Google Scholar 

  • Grupe A, Hultgren B, Ryan A, Ma YH, Bauer M, Stewart TA (1995) Transgenic knockouts reveal a critical requirement for pancreatic beta cell glucokinase in maintaining glucose homeostasis. Cell 83:69–78

    Article  PubMed  CAS  Google Scholar 

  • Inoue M, Sakuraba Y, Motegi H, Kubota N, Toki H, Matsui J, Toyoda Y, Miwa I, Terauchi Y, Kadowaki T, Shigeyama Y, Kasuga M, Adachi T, Fujimoto N, Matsumoto R, Tsuchihashi K, Kagami T, Inoue A, Kaneda H, Ishijima J, Masuya H, Suzuki T, Wakana S, Gondo Y, Minowa O, Shiroishi T, Noda T (2004) A series of maturity onset diabetes of the young, type 2 (MODY2) mouse models generated by a large-scale ENU mutagenesis program. Hum Mol Genet 13:1147–1157

    Article  PubMed  CAS  Google Scholar 

  • Ishimori N, Li R, Kelmenson PM, Korstanje R, Walsh KA, Churchill GA, Forsman-Semb K, Paigen B (2004) Quantitative trait loci that determine plasma lipids and obesity in C57BL/6J and 129S1/SvImJ inbred mice. J Lipid Res 45:1624–1632

    Article  PubMed  CAS  Google Scholar 

  • Joshi RL, Lamothe B, Cordonnier N, Mesbah K, Monthioux E, Jami J, Bucchini D (1996) Targeted disruption of the insulin receptor gene in the mouse results in neonatal lethality. EMBO J 15:1542–1547

    PubMed  CAS  Google Scholar 

  • Kiess W, Bottner A, Raile K, Kapellen T, Muller G, Galler A, Paschke R, Wabitsch M (2003) Type 2 diabetes mellitus in children and adolescents: a review from a European perspective. Horm Res 59(Suppl 1):77–84

    Article  PubMed  CAS  Google Scholar 

  • Kim JK, Michael MD, Previs SF, Peron OD, Mauvais-Jarvis F, Neschen S, Kahn BB, Kahn CR, Shulman GI (2000) Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle. J Clin Invest 105:1791–1797

    Article  PubMed  CAS  Google Scholar 

  • Kitada K, Ishishita S, Tosaka K, Takahashi R, Ueda M, Keng VW, Horie K, Takeda J (2007) Transposon-tagged mutagenesis in the rat. Nat Methods 4:131–133

    Article  PubMed  CAS  Google Scholar 

  • Kos CH (2004) Cre/loxP system for generating tissue-specific knockout mouse models. Nutr Rev 62:243–246

    PubMed  Google Scholar 

  • Krook A, Brueton L, O’Rahilly S (1993) Homozygous nonsense mutation in the insulin receptor gene in infant with leprechaunism. Lancet 342:277–278

    Article  PubMed  CAS  Google Scholar 

  • Kulkarni RN, Almind K, Goren HJ, Winnay JN, Ueki K, Okada T, Kahn CR (2003) Impact of genetic background on development of hyperinsulinemia and diabetes in insulin receptor/insulin receptor substrate-1 double heterozygous mice. Diabetes 52:1528–1534

    Article  PubMed  CAS  Google Scholar 

  • Lin HV, Accili D (2011) Reconstitution of insulin action in muscle, white adipose tissue, and brain of insulin receptor knock-out mice fails to rescue diabetes. J Biol Chem 286:9797–9804

    Article  PubMed  CAS  Google Scholar 

  • Lioubinski O, Muller M, Wegner M, Sander M (2003) Expression of Sox transcription factors in the developing mouse pancreas. Dev Dyn 227:402–408

    Article  PubMed  CAS  Google Scholar 

  • Maassen JA, Tobias ES, Kayserilli H, Tukel T, Yuksel-Apak M, D’haens E, Kleije WJ, Fery F, Van Der Zon GC (2003) Identification and functional assessment of novel and known insulin receptor mutations in five patients with syndromes of severe insulin resistance. J Clin Endocrinol Metab 88:4251–4257

    Article  PubMed  CAS  Google Scholar 

  • Matschinsky FM (1990) Glucokinase as glucose sensor and metabolic signal generator in pancreatic beta-cells and hepatocytes. Diabetes 39:647–652

    Article  PubMed  CAS  Google Scholar 

  • Matschinsky FM (2009) Assessing the potential of glucokinase activators in diabetes therapy. Nat Rev Drug Discov 8:399–416

    Article  PubMed  CAS  Google Scholar 

  • McCarthy MI (2010) Genomics, type 2 diabetes, and obesity. N Engl J Med 363:2339–2350

    Article  PubMed  CAS  Google Scholar 

  • Medici F, Hawa M, Ianari A, Pyke DA, Leslie RD (1999) Concordance rate for type II diabetes mellitus in monozygotic twins: actuarial analysis. Diabetologia 42:146–150

    Article  PubMed  CAS  Google Scholar 

  • Michael MD, Kulkarni RN, Postic C, Previs SF, Shulman GI, Magnuson MA, Kahn CR (2000) Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol Cell 6:87–97

    PubMed  CAS  Google Scholar 

  • Nissen SE, Wolski K (2010) Rosiglitazone revisited: an updated meta-analysis of risk for myocardial infarction and cardiovascular mortality. Arch Intern Med 170(14):1191–1201

    Article  PubMed  CAS  Google Scholar 

  • Nyenwe EA, Jerkins TW, Umpierrez GE, Kitabchi AE (2011) Management of type 2 diabetes: evolving strategies for the treatment of patients with type 2 diabetes. Metabolism 60:1–23

    Article  PubMed  CAS  Google Scholar 

  • Olson H, Betton G, Robinson D, Thomas K, Monro A, Kolaja G, Lilly P, Sanders J, Sipes G, Bracken W, Dorato M, Van Deun K, Smith P, Berger B, Heller A (2000) Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul Toxicol Pharmacol 32:56–67

    Article  PubMed  CAS  Google Scholar 

  • Osbak KK, Colclough K, Saint-Martin C, Beer NL, Bellanne-Chantelot C, Ellard S, Gloyn AL (2009) Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia. Hum Mutat 30:1512–1526

    Article  PubMed  CAS  Google Scholar 

  • Peters T, Ausmeier K, Ruther U (1999) Cloning of Fatso (Fto), a novel gene deleted by the Fused toes (Ft) mouse mutation. Mamm Genome 10:983–986

    Article  PubMed  CAS  Google Scholar 

  • Peyrot M, Rubin RR, Lauritzen T, Skovlund SE, Snoek FJ, Matthews DR, Landgraf R, Kleinebreil L (2005) Resistance to insulin therapy among patients and providers: results of the cross-national Diabetes Attitudes, Wishes, and Needs (DAWN) study. Diabetes Care 28:2673–2679

    Article  PubMed  Google Scholar 

  • Pino MF, Kim KA, Shelton KD, Lindner J, Odili S, Li C, Collins HW, Shiota M, Matschinsky FM, Magnuson MA (2007) Glucokinase thermolability and hepatic regulatory protein binding are essential factors for predicting the blood glucose phenotype of missense mutations. J Biol Chem 282:13906–13916

    Article  PubMed  CAS  Google Scholar 

  • Pontiroli AE (2004) Type 2 diabetes mellitus is becoming the most common type of diabetes in school children. Acta Diabetol 41:85–90

    Article  PubMed  CAS  Google Scholar 

  • Postic C, Shiota M, Niswender KD, Jetton TL, Chen Y, Moates JM, Shelton KD, Lindner J, Cherrington AD, Magnuson MA (1999) Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic beta cell-specific gene knock-outs using Cre recombinase. J Biol Chem 274:305–315

    Article  PubMed  CAS  Google Scholar 

  • Poulsen P, Kyvik KO, Vaag A, Beck-Nielsen H (1999) Heritability of type II (non-insulin-dependent) diabetes mellitus and abnormal glucose tolerance–a population-based twin study. Diabetologia 42:139–145

    Article  PubMed  CAS  Google Scholar 

  • Quwailid MM, Hugill A, Dear N, Vizor L, Wells S, Horner E, Fuller S, Weedon J, Mcmath H, Woodman P, Edwards D, Campbell D, Rodger S, Carey J, Roberts A, Glenister P, Lalanne Z, Parkinson N, Coghill EL, Mckeone R, Cox S, Willan J, Greenfield A, Keays D, Brady S, Spurr N, Gray I, Hunter J, Brown SD, Cox RD (2004) A gene-driven ENU-based approach to generating an allelic series in any gene. Mamm Genome 15:585–591

    Article  PubMed  CAS  Google Scholar 

  • Ragvin A, Moro E, Fredman D, Navratilova P, Drivenes O, Engstrom PG, Alonso ME, De La Calle Mustienes E, Gomez Skarmeta JL, Tavares MJ, Casares F, Manzanares M, Van Heyningen V, Molven A, Njolstad PR, Argenton F, Lenhard B, Becker TS (2010) Long-range gene regulation links genomic type 2 diabetes and obesity risk regions to HHEX, SOX4, and IRX3. Proc Natl Acad Sci USA 107:775–780

    Article  PubMed  CAS  Google Scholar 

  • Ray MK, Fagan SP, Brunicardi FC (2000) The Cre-loxP system: a versatile tool for targeting genes in a cell- and stage-specific manner. Cell Transpl 9:805–815

    CAS  Google Scholar 

  • Reed DR, Li X, McDaniel AH, Lu K, Li S, Tordoff MG, Price RA, Bachmanov AA (2003) Loci on chromosomes 2, 4, 9, and 16 for body weight, body length, and adiposity identified in a genome scan of an F2 intercross between the 129P3/J and C57BL/6ByJ mouse strains. Mamm Genome 14:302–313

    Article  PubMed  CAS  Google Scholar 

  • Rerup CC (1970) Drugs producing diabetes through damage of the insulin secreting cells. Pharmacol Rev 22:485–518

    PubMed  CAS  Google Scholar 

  • Sauer B (1998) Inducible gene targeting in mice using the Cre/lox system. Methods 14:381–392

    Article  PubMed  CAS  Google Scholar 

  • Saxena R, Voight BF, Lyssenko V, Burtt NP, De Bakker PI, Chen H, Roix JJ, Kathiresan S, Hirschhorn JN, Daly MJ, Hughes TE, Groop L, Altshuler D, Almgren P, Florez JC, Meyer J, Ardlie K, Bengtsson Bostrom K, Isomaa B, Lettre G, Lindblad U, Lyon HN, Melander O, Newton-Cheh C, Nilsson P, Orho-Melander M, Rastam L, Speliotes EK, Taskinen MR, Tuomi T, Guiducci C, Berglund A, Carlson J, Gianniny L, Hackett R, Hall L, Holmkvist J, Laurila E, Sjogren M, Sterner M, Surti A, Svensson M, Tewhey R, Blumenstiel B, Parkin M, Defelice M, Barry R, Brodeur W, Camarata J, Chia N, Fava M, Gibbons J, Handsaker B, Healy C, Nguyen K, Gates C, Sougnez C, Gage D, Nizzari M, Gabriel SB, Chirn GW, Ma Q, Parikh H, Richardson D, Ricke D, Purcell S (2007) Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316:1331–1336

    Article  PubMed  CAS  Google Scholar 

  • Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, Duren WL, Erdos MR, Stringham HM, Chines PS, Jackson AU, Prokunina-Olsson L, Ding CJ, Swift AJ, Narisu N, Hu T, Pruim R, Xiao R, Li XY, Conneely KN, Riebow NL, Sprau AG, Tong M, White PP, Hetrick KN, Barnhart MW, Bark CW, Goldstein JL, Watkins L, Xiang F, Saramies J, Buchanan TA, Watanabe RM, Valle TT, Kinnunen L, Abecasis GR, Pugh EW, Doheny KF, Bergman RN, Tuomilehto J, Collins FS, Boehnke M (2007) A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316:1341–1345

    Article  PubMed  CAS  Google Scholar 

  • Shultz LD, Ishikawa F, Greiner DL (2007) Humanized mice in translational biomedical research. Nat Rev Immunol 7:118–130

    Article  PubMed  CAS  Google Scholar 

  • Singh S, Loke YK, Furberg CD (2007) Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. JAMA 298:1189–1195

    Article  PubMed  CAS  Google Scholar 

  • Song SH, Hardisty CA (2008) Early-onset type 2 diabetes mellitus: an increasing phenomenon of elevated cardiovascular risk. Expert Rev Cardiovasc Ther 6:315–322

    Article  PubMed  Google Scholar 

  • Stanford WL, Cohn JB, Cordes SP (2001) Gene-trap mutagenesis: past, present and beyond. Nat Rev Genet 2:756–768

    Article  PubMed  CAS  Google Scholar 

  • Surwit RS, Kuhn CM, Cochrane C, McCubbin JA, Feinglos MN (1988) Diet-induced type II diabetes in C57BL/6J mice. Diabetes 37:1163–1167

    Article  PubMed  CAS  Google Scholar 

  • Tateno C, Yoshizane Y, Saito N, Kataoka M, Utoh R, Yamasaki C, Tachibana A, Soeno Y, Asahina K, Hino H, Asahara T, Yokoi T, Furukawa T, Yoshizato K (2004) Near completely humanized liver in mice shows human-type metabolic responses to drugs. Am J Pathol 165:901–912

    Article  PubMed  CAS  Google Scholar 

  • Toye AA, Moir L, Hugill A, Bentley L, Quarterman J, Mijat V, Hough T, Goldsworthy M, Haynes A, Hunter AJ, Browne M, Spurr N, Cox RD (2004) A new mouse model of type 2 diabetes, produced by N-ethyl-nitrosourea mutagenesis, is the result of a missense mutation in the glucokinase gene. Diabetes 53:1577–1583

    Article  PubMed  CAS  Google Scholar 

  • Tugwood JD, Montague CT (2002) Biology and toxicology of PPARgamma ligands. Hum Exp Toxicol 21:429–437

    Article  PubMed  CAS  Google Scholar 

  • Vassilopoulos S, Esk C, Hoshino S, Funke BH, Chen CY, Plocik AM, Wright WE, Kucherlapati R, Brodsky FM (2009) A role for the CHC22 clathrin heavy-chain isoform in human glucose metabolism. Science 324:1192–1196

    Article  PubMed  CAS  Google Scholar 

  • Vaxillaire M, Froguel P (2008) Monogenic diabetes in the young, pharmacogenetics and relevance to multifactorial forms of type 2 diabetes. Endocr Rev 29:254–264

    Article  PubMed  CAS  Google Scholar 

  • Vionnet N, Stoffel M, Takeda J, Yasuda K, Bell GI, Zouali H, Lesage S, Velho G, Iris F, Passa P et al (1992) Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus. Nature 356:721–722

    Article  PubMed  CAS  Google Scholar 

  • Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447:661–678

    Article  Google Scholar 

  • Wertheimer E, Lu SP, Backeljauw PF, Davenport ML, Taylor SI (1993) Homozygous deletion of the human insulin receptor gene results in leprechaunism. Nat Genet 5:71–73

    Article  PubMed  CAS  Google Scholar 

  • Weyer C, Bogardus C, Mott DM, Pratley RE (1999) The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest 104:787–794

    Article  PubMed  CAS  Google Scholar 

  • Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:1047–1053

    Article  PubMed  Google Scholar 

  • Wilson ME, Yang KY, Kalousova A, Lau J, Kosaka Y, Lynn FC, Wang J, Mrejen C, Episkopou V, Clevers HC, German MS (2005) The HMG box transcription factor Sox4 contributes to the development of the endocrine pancreas. Diabetes 54:3402–3409

    Article  PubMed  CAS  Google Scholar 

  • World Health Organization and International Diabetes Federation (2006) Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: report of a WHO/IDF consultation, 1 Nov 2006. WHO Press, Geneva. http://www.who.int/diabetes/publications/Definition%20and%20diagnosis%20of%20diabetes_new.pdf

  • Xu X, Yavar Z, Verdin M, Ying Z, Mihai G, Kampfrath T, Wang A, Zhong M, Lippmann M, Chen LC, Rajagopalan S, Sun Q (2010) Effect of early particulate air pollution exposure on obesity in mice:role of p47phox. Arterioscler Thromb Vasc Biol 30:2518–2527

    Article  PubMed  CAS  Google Scholar 

  • 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 21:645–651

    Article  PubMed  CAS  Google Scholar 

  • Zimmet P, Alberti KG, Shaw J (2001) Global and societal implications of the diabetes epidemic. Nature 414:782–787

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. MRC Harwell, Metabolism and Inflammation, Harwell Oxford Campus, Oxfordshire, UK

    Fiona McMurray & Roger D. Cox

Authors
  1. Fiona McMurray
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roger D. Cox
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roger D. Cox.

Rights and permissions

Reprints and permissions

About this article

Cite this article

McMurray, F., Cox, R.D. Mouse models and type 2 diabetes: translational opportunities. Mamm Genome 22, 390–400 (2011). https://doi.org/10.1007/s00335-011-9345-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00335-011-9345-3

Keywords

Search

Navigation