JAX
Mouse Strain Datasheet - 004421
B6;129-Irs2tm1Mfw/J
Also Known As: IRS-2 KO
These Irs2 knock-out mice exhibit a progressive development of a type 2 diabetic phenotype.
Donating Investigator
Dr. Michael J. Grusby, Harvard Medical School
Genetic overview
| Genetic Background | Generation |
|---|---|
|
|
Irs2tm1Mfw
| Allele Type | Gene Symbol | Gene Name |
|---|---|---|
| Targeted (Null/Knockout) | Irs2 | insulin receptor substrate 2 |
Detailed Description
Mice homozygous for the targeted allele are viable yet sterile and exhibit a progressive development of a type 2 diabetic phenotype. At birth, mice are slightly (10%) smaller than wildtype littermates. This weight difference is maintained from birth through adulthood. Elevated blood sugar levels can be detected by 3 days of age. By 3-6 weeks of age mice develop fasting hyperglycemia and become diabetic by 10 weeks. A reduced beta-cell mass can be detected by 4 weeks and a profound insulin resistance is observed in skeletal muscle and liver tissue by 6-8 weeks. Levels of fasting sugars continue to rise until male mice eventually succumb to dehydration and hyperosomolar coma. Female mice, while exhibiting a similar progression, tend not to die. This mutant mouse represents a model useful in studies related to type 2 diabetes.
Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to delete the entire insulin receptor 2 gene. The construct was electroporated into 129X1/SvJ x 129S1/Sv-derived R1 embryonic stem (ES) cells in the laboratory of Dr. Morris White, Joslin Diabetes Center/HHMI, Boston. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice.
Control Suggestions
Selected References
- Withers DJ; Gutierrez JS; Towery H; Burks DJ; Ren JM; Previs S; Zhang Y; Bernal D; Pons S; Shulman GI; Bonner-Weir S; White MF. 1998. Disruption of IRS-2 causes type 2 diabetes in mice. Nature 391(6670):900-4. PubMed: 9495343MGI: J:46134
Irs2tm1Mfw
Allele Symbol: Irs2tm1Mfw
| Allele Name | targeted mutation 1, Morris F White |
|---|---|
| Allele Type | Targeted (Null/Knockout) |
| Allele Synonym(s) | Irs2- |
| Gene Symbol and Name | Irs2, insulin receptor substrate 2 |
| Gene Synonym(s) | 4PS; IRS-2; Irs-2 |
| Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl<+> |
| Chromosome | 8 |
| Molecular Note | A targeting vector containing a PGK-neomycin cassette replaced the entire gene. Lack of protein was demonstrated in liver and muscle extracts by Western analysis in homozygous mutant animals. |
| Mutations Made By | Morris White, Joslin Diabetes Center/HHMI |
Disease Terms
Research Areas By Genotype
This mouse can be used to support research in many areas including:
Genotype: Irs2tm1Mfw related
- Diabetes and Obesity Research
- Insulin Receptors and Growth Factors
- Type 2 Diabetes (NIDDM)
Mammalian Phenotype Terms by Genotype
Genotype: Irs2tm1Mfw/Irs2tm1Mfw
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
cellular phenotype
- decreased oocyte number
- at E18.5, mutant ovaries contain decreased numbers of primary oocytes relative to wild-type ovaries (MGI Ref ID J:64791)
mortality/aging
- premature death
homeostasis/metabolism phenotype
- abnormal circulating glucose level
- abnormal circulating hormone level
- (MGI Ref ID J:64791)
- abnormal circulating insulin level
- elevated serum insulin levels at 6 weeks (before diabetes developed) and decreased insulin levels at 8 weeks with the onset of diabetes (MGI Ref ID J:94000)
- abnormal energy homeostasis
- females homozygotes show hypothalamic resistance to leptin, suggesting defects in homeostatic mechanisms involved in leptin sensing and/or signaling (MGI Ref ID J:64791)
- abnormal glucose homeostasis
- homozygous males are more severely affected than age-matched females with respect to abnormal glucose homeostasis (MGI Ref ID J:64791)
- however, insulin-stimulated, phosphotyrosine-associated PI 3-kinase response after exercise is slightly higher than the insulin-stimulated response alone (MGI Ref ID J:74303)
- immediately after treadmill exercise, male homozygotes show an attenuated increase in insulin-stimulated, phosphotyrosine-associated PI 3-kinase activity relative to wild-type males (MGI Ref ID J:74303)
- abnormal lipid homeostasis
- dyslipidemia (MGI Ref ID J:96047)
- decreased circulating estradiol level
- female homozygotes display reduced plasma estradiol levels relative to wild-type females in both dioestrous and oestrous states (MGI Ref ID J:64791)
- decreased circulating luteinizing hormone level
- surprisingly, female homozygotes display low plasma luteinizing hormone levels relative to wild-type females in both dioestrous and oestrous states (MGI Ref ID J:64791)
- decreased circulating progesterone level
- female homozygotes display reduced plasma progesterone levels relative to wild-type females in both dioestrous and oestrous states (MGI Ref ID J:64791)
- decreased circulating prolactin level
- female homozygotes display low plasma prolactin levels relative to wild-type females (MGI Ref ID J:64791)
- decreased circulating testosterone level
- female homozygotes display reduced plasma testosterone levels relative to wild-type females in both dioestrous and oestrous states (MGI Ref ID J:64791)
- decreased glycogen level
- hyperglycemia
- at 10 weeks, homozygotes exhibit overt diabetes with fasting glucose levels of 323 35 mg dl-1; if left untreated, the fasting sugar levels rise progressively to >400 mg dl-1 at 12-16 weeks of age (MGI Ref ID J:46134)
- developed a progressive increase with severe hyperglycemia (MGI Ref ID J:135659)
- developed in males between 4 and 6 weeks of age, which progressed to overt diabetes during the next 5-6 weeks until they died (MGI Ref ID J:94000)
- fasting glucose levels were higher than in wild-type mice (MGI Ref ID J:135659)
- homozygotes show increased levels of randomly fed sugars at postnatal day 3, and fasting hyperglycemia between 3 and 6 weeks of age (MGI Ref ID J:46134)
- seen at about 10 weeks of age (MGI Ref ID J:96047)
- impaired glucose tolerance
- at 6-8 weeks, homozygotes display significant glucose intolerance (>95% penetrance) during an intraperitoneal glucose-tolerance test (MGI Ref ID J:46134)
- by 6 weeks, male homozygotes are severely glucose intolerant (MGI Ref ID J:64791)
- in contrast, age-matched female homozygotes show only slightly increased blood glucose levels and mildly impaired glucose tolerance, suggesting sexual dimorphism in the diabetic phenotype (MGI Ref ID J:64791)
- increased circulating insulin level
- at >6 weeks, homozygotes display a 3-fold increase in fasting insulin levels relative to wild-type mice (MGI Ref ID J:46134)
- both fasting and fed insulin levels were higher than in wild-type mice (MGI Ref ID J:135659)
- despite fasting hyperinsulinemia, homozygotes respond with a nearly 2-fold increase in insulin levels 60 minutes after glucose loading (MGI Ref ID J:46134)
- increased circulating leptin level
- insulin resistance
behavior/neurological phenotype
- abnormal mating frequency
- only 18.2% of female homozygotes vs 100% of wild-type display copulation plugs, suggesting abnormal oestrous cycle and sexual behavior (MGI Ref ID J:64791)
- polydipsia
- (MGI Ref ID J:46134)
- polyphagia
- female homozygotes consume 30% more chow relative to wild-type females (MGI Ref ID J:64791)
renal/urinary system phenotype
- polyuria
- homozygotes display polyuria without ketosis (MGI Ref ID J:46134)
endocrine/exocrine gland phenotype
- abnormal ovarian follicle morphology
- at 6 weeks, mutant ovaries contain very few surface follicles and show thickening of the cortex relative to wild-type (MGI Ref ID J:64791)
- abnormal pancreatic beta cell morphology
- individual beta cell size is decreased (MGI Ref ID J:96047)
- absent corpus luteum
- mutant ovaries show an almost complete absence of corpora lutea (MGI Ref ID J:64791)
- decreased gonadotroph cell number
- mutant pituitaries contain ~40% less gonadotrophs than wild-type pituitaries (MGI Ref ID J:64791)
- decreased pancreatic beta cell mass
- at 4 weeks, homozygotes show a significant reduction in pancreatic beta-cell mass indicating failure of compensatory islet hyperplasia (MGI Ref ID J:46134)
- decreased beta cell proliferation and increased beta cell accounts for reduction in beta cell mass (MGI Ref ID J:135659)
- no significant difference in non-beta endocrine-cell mass is observed (MGI Ref ID J:46134)
- reduced beta cell mass compared to wild-type (MGI Ref ID J:135659)
- decreased pancreatic beta cell number
- at 8 weeks, islet area reduced by threefold due to 50% fewer beta cells (MGI Ref ID J:94000)
- impaired ovarian folliculogenesis
- adult mutant ovaries contain reduced numbers of primary follicles with few growing follicles reaching an antral phase of development (MGI Ref ID J:64791)
- small ovary
- at 6 weeks, female homozygotes show normal development of the external genitalia and reproductive tract; however, mutant ovaries are small relative to wild-type (MGI Ref ID J:64791)
- small pancreatic islets
- islet mass and density are significantly decreased compared to wild-type mice (MGI Ref ID J:96047)
- small pituitary gland
- mutant pituitaries are ~30% smaller (MGI Ref ID J:64791)
- small pituitary intermediate lobe
- the size of the intermediate lobe is reduced more than that of other lobes (MGI Ref ID J:74303)
growth/size/body region phenotype
- decreased birth body size
- homozygous neonates are 10% smaller than heterozygous or wild-type littermates (MGI Ref ID J:46134)
- decreased body weight
- obese
- female homozygotes weigh 20% more than wild-type females and are obese despite elevated leptin levels (MGI Ref ID J:64791)
- weight loss
- mice gained weight until about 9 weeks, and began to decline (MGI Ref ID J:135659)
nervous system phenotype
- decreased gonadotroph cell number
- mutant pituitaries contain ~40% less gonadotrophs than wild-type pituitaries (MGI Ref ID J:64791)
- small pituitary gland
- mutant pituitaries are ~30% smaller (MGI Ref ID J:64791)
- small pituitary intermediate lobe
- the size of the intermediate lobe is reduced more than that of other lobes (MGI Ref ID J:74303)
reproductive system phenotype
- abnormal oogenesis
- (MGI Ref ID J:64791)
- abnormal ovarian follicle morphology
- at 6 weeks, mutant ovaries contain very few surface follicles and show thickening of the cortex relative to wild-type (MGI Ref ID J:64791)
- abnormal ovulation
- absent corpus luteum
- mutant ovaries show an almost complete absence of corpora lutea (MGI Ref ID J:64791)
- absent estrous cycle
- 61% of female homozygotes fail to cycle and remain in an inactive or dioestrous state (MGI Ref ID J:64791)
- anovulation
- female homozygotes show features of anovulation, such as thickening of the ovarian stroma and absence of corpora lutea (MGI Ref ID J:64791)
- decreased oocyte number
- at E18.5, mutant ovaries contain decreased numbers of primary oocytes relative to wild-type ovaries (MGI Ref ID J:64791)
- female infertility
- at <10 weeks, female homozygotes are relatively euglycemic and mildly insulin resistant, suggesting that female infertility is not a direct result of impaired glucose metabolism (MGI Ref ID J:64791)
- when bred with homozygous mutant males, 0% of homozygous virgin females become pregnant during an 8-week period (MGI Ref ID J:64791)
- impaired ovarian folliculogenesis
- adult mutant ovaries contain reduced numbers of primary follicles with few growing follicles reaching an antral phase of development (MGI Ref ID J:64791)
- reduced female fertility
- when bred with wild-type males, only 9% of homozygous virgin females (4?6-week-old) become pregnant during an 8-week period (MGI Ref ID J:64791)
- reduced male fertility
- male homozygotes exhibit reduced fertility; males are adequate breeders only if mated prior to the onset of severe diabetes (MGI Ref ID J:64791)
- small ovary
- at 6 weeks, female homozygotes show normal development of the external genitalia and reproductive tract; however, mutant ovaries are small relative to wild-type (MGI Ref ID J:64791)
adipose tissue phenotype
- increased total body fat amount
- female homozygotes store twice as much body fat as age-matched wild-type females (MGI Ref ID J:64791)
References
- Withers DJ; Gutierrez JS; Towery H; Burks DJ; Ren JM; Previs S; Zhang Y; Bernal D; Pons S; Shulman GI; Bonner-Weir S; White MF. 1998. Disruption of IRS-2 causes type 2 diabetes in mice. Nature 391(6670):900-4. PubMed: 9495343MGI: J:46134
Additional - Irs2tm1Mfw related
- Albert-Fort M; Hombrebueno JR; Pons-Vazquez S; Sanz-Gonzalez S; Diaz-Llopis M; Pinazo-Duran MD. 2014. Retinal neurodegenerative changes in the adult insulin receptor substrate-2 deficient mouse. Exp Eye Res 124:1-10. PubMed: 24792588MGI: J:229846
- Alvarez-Perez JC; Rosa TC; Casinelli GP; Valle SR; Lakshmipathi J; Rosselot C; Rausell-Palamos F; Vasavada RC; Garcia-Ocana A. 2014. Hepatocyte growth factor ameliorates hyperglycemia and corrects beta-cell mass in IRS2-deficient mice. Mol Endocrinol 28(12):2038-48. PubMed: 25361392MGI: J:218271
- Arroba AI; Revuelta-Cervantes J; Menes L; Gonzalez-Rodriguez A; Pardo V; de la Villa P; Burks DJ; Valverde AM. 2013. Loss of protein tyrosine phosphatase 1B increases IGF-I receptor tyrosine phosphorylation but does not rescue retinal defects in IRS2-deficient mice. Invest Ophthalmol Vis Sci 54(6):4215-25. PubMed: 23702782MGI: J:214039
- Baquedano E; Burgos-Ramos E; Canelles S; Gonzalez-Rodriguez A; Chowen JA; Argente J; Barrios V; Valverde AM; Frago LM. 2016. Increased oxidative stress and apoptosis in the hypothalamus of diabetic male mice in the insulin receptor substrate-2 knockout model. Dis Model Mech 9(5):573-83. PubMed: 27013528MGI: J:232488
- Burgos-Ramos E; Gonzalez-Rodriguez A; Canelles S; Baquedano E; Frago LM; Revuelta-Cervantes J; Gomez-Ambrosi J; Fruhbeck G; Chowen JA; Argente J; Valverde AM; Barrios V. 2012. Differential insulin receptor substrate-1 (IRS1)-related modulation of neuropeptide Y and proopiomelanocortin expression in nondiabetic and diabetic IRS2-/- mice. Endocrinology 153(3):1129-40. PubMed: 22210743MGI: J:182437
- Burks DJ; de Mora JF; Schubert M; Withers DJ; Myers MG; Towery HH; Altamuro SL; Flint CL; White MF. 2000. IRS-2 pathways integrate female reproduction and energy homeostasis. Nature 407(6802):377-82. PubMed: 11014193MGI: J:64791
- Carew RM; Sadagurski M; Goldschmeding R; Martin F; White MF; Brazil DP. 2010. Deletion of Irs2 causes reduced kidney size in mice: role for inhibition of GSK3beta? BMC Dev Biol 10:73. PubMed: 20604929MGI: J:163851
- Chirivella L; Cano-Jaimez M; Perez-Sanchez F; Herraez L; Carretero J; Farinas I; Burks DJ; Kirstein M. 2012. IRS2 signalling is required for the development of a subset of sensory spinal neurons. Eur J Neurosci 35(3):341-52. PubMed: 22288475MGI: J:184234
- Garcia-Barrado MJ; Iglesias-Osma MC; Moreno-Viedma V; Pastor Mansilla MF; Gonzalez SS; Carretero J; Moratinos J; Burks DJ. 2011. Differential sensitivity to adrenergic stimulation underlies the sexual dimorphism in the development of diabetes caused by Irs-2 deficiency. Biochem Pharmacol 81(2):279-88. PubMed: 20959116MGI: J:167776
- Gonzalez-Navarro H; Vinue A; Vila-Caballer M; Fortuno A; Beloqui O; Zalba G; Burks D; Diez J; Andres V. 2008. Molecular mechanisms of atherosclerosis in metabolic syndrome: role of reduced IRS2-dependent signaling. Arterioscler Thromb Vasc Biol 28(12):2187-94. PubMed: 18802016MGI: J:159794
- Gonzalez-Rodriguez A; Mas Gutierrez JA; Sanz-Gonzalez S; Ros M; Burks DJ; Valverde AM. 2010. Inhibition of PTP1B restores IRS1-mediated hepatic insulin signaling in IRS2-deficient mice. Diabetes 59(3):588-99. PubMed: 20028942MGI: J:164152
- Griffeth RJ; Carretero J; Burks DJ. 2013. Insulin receptor substrate 2 is required for testicular development. PLoS One 8(5):e62103. PubMed: 23741292MGI: J:200785
- Hennige AM; Burks DJ; Ozcan U; Kulkarni RN; Ye J; Park S; Schubert M; Fisher TL; Dow MA; Leshan R; Zakaria M; Mossa-Basha M; White MF. 2003. Upregulation of insulin receptor substrate-2 in pancreatic beta cells prevents diabetes. J Clin Invest 112(10):1521-32. PubMed: 14617753MGI: J:94000
- Howlett KF; Sakamoto K; Hirshman MF; Aschenbach WG; Dow M; White MF; Goodyear LJ. 2002. Insulin signaling after exercise in insulin receptor substrate-2-deficient mice. Diabetes 51(2):479-83. PubMed: 11812758MGI: J:74303
- Jain S; Ruiz de Azua I; Lu H; White MF; Guettier JM; Wess J. 2013. Chronic activation of a designer G(q)-coupled receptor improves beta cell function. J Clin Invest 123(4):1750-62. PubMed: 23478411MGI: J:197536
- Kido Y; Burks DJ; Withers D; Bruning JC; Kahn CR; White MF; Accili D. 2000. Tissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1, and IRS-2. J Clin Invest 105(2):199-205. PubMed: 10642598MGI: J:59431
- Killick R; Scales G; Leroy K; Causevic M; Hooper C; Irvine EE; Choudhury AI; Drinkwater L; Kerr F; Al-Qassab H; Stephenson J; Yilmaz Z; Giese KP; Brion JP; Withers DJ; Lovestone S. 2009. Deletion of Irs2 reduces amyloid deposition and rescues behavioural deficits in APP transgenic mice. Biochem Biophys Res Commun 386(1):257-62. PubMed: 19523444MGI: J:150650
- Kim JJ; Kido Y; Scherer PE; White MF; Accili D. 2007. Analysis of compensatory beta-cell response in mice with combined mutations of Insr and Irs2. Am J Physiol Endocrinol Metab 292(6):E1694-701. PubMed: 17299086MGI: J:121915
- Kitamura T; Nakae J; Kitamura Y; Kido Y; Biggs WH 3rd; Wright CV; White MF; Arden KC; Accili D. 2002. The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth. J Clin Invest 110(12):1839-47. PubMed: 12488434MGI: J:80826
- Kitamura YI; Kitamura T; Kruse JP; Raum JC; Stein R; Gu W; Accili D. 2005. FoxO1 protects against pancreatic beta cell failure through NeuroD and MafA induction. Cell Metab 2(3):153-63. PubMed: 16154098MGI: J:129682
- Kushner JA; Haj FG; Klaman LD; Dow MA; Kahn BB; Neel BG; White MF. 2004. Islet-Sparing Effects of Protein Tyrosine Phosphatase-1b Deficiency Delays Onset of Diabetes in IRS2 Knockout Mice. Diabetes 53(1):61-66. PubMed: 14693698MGI: J:87249
- Kushner JA; Simpson L; Wartschow LM; Guo S; Rankin MM; Parsons R; White MF. 2005. Phosphatase and tensin homolog regulation of islet growth and glucose homeostasis. J Biol Chem 280(47):39388-93. PubMed: 16170201MGI: J:104109
- Kushner JA; Ye J; Schubert M; Burks DJ; Dow MA; Flint CL; Dutta S; Wright CV; Montminy MR; White MF. 2002. Pdx1 restores beta cell function in Irs2 knockout mice. J Clin Invest 109(9):1193-201. PubMed: 11994408MGI: J:76408
- Martin ED; Sanchez-Perez A; Trejo JL; Martin-Aldana JA; Cano Jaimez M; Pons S; Acosta Umanzor C; Menes L; White MF; Burks DJ. 2012. IRS-2 Deficiency Impairs NMDA Receptor-Dependent Long-term Potentiation. Cereb Cortex 22(8):1717-27. PubMed: 21955917MGI: J:185333
- Martinez-Hervas S; Vinue A; Nunez L; Andres-Blasco I; Piqueras L; Real JT; Ascaso JF; Burks DJ; Sanz MJ; Gonzalez-Navarro H. 2014. Insulin resistance aggravates atherosclerosis by reducing vascular smooth muscle cell survival and increasing CX3CL1/CX3CR1 axis. Cardiovasc Res 103(2):324-36. PubMed: 24788416MGI: J:229852
- Nakae J; Biggs WH; Kitamura T; Cavenee WK; Wright CV; Arden KC; Accili D. 2002. Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1. Nat Genet 32(2):245-53. PubMed: 12219087MGI: J:79560
- Oliveira JM; Rebuffat SA; Gasa R; Burks DJ; Garcia A; Kalko SG; Zafra D; Guinovart JJ; Gomis R. 2014. Tungstate promotes beta-cell survival in Irs2-/- mice. Am J Physiol Endocrinol Metab 306(1):E36-47. PubMed: 24253047MGI: J:208382
- Ren D; Sun J; Mao L; Ye H; Polonsky KS. 2014. BH3-only molecule Bim mediates beta-cell death in IRS2 deficiency. Diabetes 63(10):3378-87. PubMed: 24760140MGI: J:229863
- Roncero I; Alvarez E; Acosta C; Sanz C; Barrio P; Hurtado-Carneiro V; Burks D; Blazquez E. 2013. Insulin-receptor substrate-2 (irs-2) is required for maintaining glucokinase and glucokinase regulatory protein expression in mouse liver. PLoS One 8(4):e58797. PubMed: 23560040MGI: J:199880
- Sadagurski M; Cheng Z; Rozzo A; Palazzolo I; Kelley GR; Dong X; Krainc D; White MF. 2011. IRS2 increases mitochondrial dysfunction and oxidative stress in a mouse model of Huntington disease. J Clin Invest 121(10):4070-81. PubMed: 21926467MGI: J:178490
- Sadagurski M; Weingarten G; Rhodes CJ; White MF; Wertheimer E. 2005. Insulin receptor substrate 2 plays diverse cell-specific roles in the regulation of glucose transport. J Biol Chem 280(15):14536-44. PubMed: 15705592MGI: J:107134
- Santamaria B; Marquez E; Lay A; Carew RM; Gonzalez-Rodriguez A; Welsh GI; Ni L; Hale LJ; Ortiz A; Saleem MA; Brazil DP; Coward RJ; Valverde AM. 2015. IRS2 and PTEN are key molecules in controlling insulin sensitivity in podocytes. Biochim Biophys Acta 1853(12):3224-34. PubMed: 26384875MGI: J:231397
- Schubert M; Brazil DP; Burks DJ; Kushner JA; Ye J; Flint CL; Farhang-Fallah J; Dikkes P; Warot XM; Rio C; Corfas G; White MF. 2003. Insulin receptor substrate-2 deficiency impairs brain growth and promotes tau phosphorylation. J Neurosci 23(18):7084-92. PubMed: 12904469MGI: J:84857
- Selman C; Lingard S; Choudhury AI; Batterham RL; Claret M; Clements M; Ramadani F; Okkenhaug K; Schuster E; Blanc E; Piper MD; Al-Qassab H; Speakman JR; Carmignac D; Robinson IC; Thornton JM; Gems D; Partridge L; Withers DJ. 2008. Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice. FASEB J 22(3):807-18. PubMed: 17928362MGI: J:134916
- Sobel BE; Schneider DJ; Lee YH; Pratley RE. 2006. Insulin resistance increases PAI-1 in the heart. Biochem Biophys Res Commun 346(1):102-7. PubMed: 16750510MGI: J:110785
- Swindell WR. 2009. Accelerated failure time models provide a useful statistical framework for aging research. Exp Gerontol 44(3):190-200. PubMed: 19007875MGI: J:146582
- Szabolcs M; Keniry M; Simpson L; Reid LJ; Koujak S; Schiff SC; Davidian G; Licata S; Gruvberger-Saal S; Murty VV; Nandula S; Efstratiadis A; Kushner JA; White MF; Parsons R. 2009. Irs2 inactivation suppresses tumor progression in Pten+/- mice. Am J Pathol 174(1):276-86. PubMed: 19095950MGI: J:144212
- Tanabe K; Liu Z; Patel S; Doble BW; Li L; Cras-Meneur C; Martinez SC; Welling CM; White MF; Bernal-Mizrachi E; Woodgett JR; Permutt MA. 2008. Genetic deficiency of glycogen synthase kinase-3beta corrects diabetes in mouse models of insulin resistance. PLoS Biol 6(2):e37. PubMed: 18288891MGI: J:135659
- Uchida T; Nakamura T; Hashimoto N; Matsuda T; Kotani K; Sakaue H; Kido Y; Hayashi Y; Nakayama KI; White MF; Kasuga M. 2005. Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice. Nat Med 11(2):175-82. PubMed: 15685168MGI: J:96047
- Vinue A; Andres-Blasco I; Herrero-Cervera A; Piqueras L; Andres V; Burks DJ; Sanz MJ; Gonzalez-Navarro H. 2015. Ink4/Arf locus restores glucose tolerance and insulin sensitivity by reducing hepatic steatosis and inflammation in mice with impaired IRS2-dependent signalling. Biochim Biophys Acta 1852(9):1729-42. PubMed: 26022372MGI: J:233930
- Withers DJ; Burks DJ; Towery HH; Altamuro SL; Flint CL; White MF. 1999. Irs-2 coordinates Igf-1 receptor-mediated beta-cell development and peripheral insulin signalling. Nat Genet 23(1):32-40. PubMed: 10471495MGI: J:57319
- Xuan S; Szabolcs M; Cinti F; Perincheri S; Accili D; Efstratiadis A. 2010. Genetic analysis of type-1 insulin-like growth factor receptor signaling through insulin receptor substrate-1 and -2 in pancreatic beta cells. J Biol Chem 285(52):41044-50. PubMed: 20947509MGI: J:167586
- Yi X; Schubert M; Peachey NS; Suzuma K; Burks DJ; Kushner JA; Suzuma I; Cahill C; Flint CL; Dow MA; Leshan RL; King GL; White MF. 2005. Insulin receptor substrate 2 is essential for maturation and survival of photoreceptor cells. J Neurosci 25(5):1240-8. PubMed: 15689562MGI: J:98107