Strain Name:

B6;129-Irs2tm1Mfw/J

Stock Number:

004421

Order this mouse

Availability:

Cryopreserved - Ready for recovery

Use Restrictions Apply, see Terms of Use

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
 
Donating InvestigatorDr. Michael J. Grusby,   Harvard Medical School

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 Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Diabetes Mellitus, Noninsulin-Dependent; NIDDM
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Irs2tm1Mfw/Irs2tm1Mfw

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
  • mortality/aging
  • premature death
    • male mutants die prematurely from dehydration and hyperosomolar coma   (MGI Ref ID J:46134)
    • female mutants exhibit a similar disease progression but rarely die   (MGI Ref ID J:46134)
    • death due to diabetes   (MGI Ref ID J:94000)
  • homeostasis/metabolism phenotype
  • 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)
      • 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)
        • despite fasting hyperinsulinemia, homozygotes respond with a nearly 2-fold increase in insulin levels 60 minutes after glucose loading   (MGI Ref ID J:46134)
        • both fasting and fed insulin levels were higher than in wild-type mice   (MGI Ref ID J:135659)
    • 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)
    • increased circulating leptin level
      • as early as 4 weeks (i.e. prior to the onset of abnormal glucose tolerance) female homozygotes show a 2.5-fold increase in circulating leptin levels   (MGI Ref ID J:64791)
      • at 8 weeks, circulating leptin levels are increased by >5-fold relative to wild-type levels   (MGI Ref ID J:64791)
  • 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
    • 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)
    • 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)
    • homozygous males are more severely affected than age-matched females with respect to abnormal glucose homeostasis   (MGI Ref ID J:64791)
    • abnormal circulating glucose level
      • treadmill exercise reduces blood glucose by ~20% in fasted wild-type mice but has no effect on blood glucose in fasted homozygotes   (MGI Ref ID J:74303)
      • plasma insulin concentrations are similar between wild-type and mutant mice at rest and remain unchanged after exercise   (MGI Ref ID J:74303)
      • hyperglycemia
        • 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)
        • 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)
        • seen at about 10 weeks of age   (MGI Ref ID J:96047)
        • developed a progressive increase with severe hyperglycemia   (MGI Ref ID J:135659)
        • fasting glucose levels were higher than in wild-type mice   (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)
    • 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)
      • 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)
        • despite fasting hyperinsulinemia, homozygotes respond with a nearly 2-fold increase in insulin levels 60 minutes after glucose loading   (MGI Ref ID J:46134)
        • both fasting and fed insulin levels were higher than in wild-type mice   (MGI Ref ID J:135659)
    • decreased glycogen level
      • at rest, fasted homozygotes tend to have reduced muscle glycogen levels relative to wild-type mice   (MGI Ref ID J:74303)
      • after treadmill exercise, homozygotes display significantly lower muscle glycogen levels than wild-type mice   (MGI Ref ID J:74303)
    • 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)
    • insulin resistance
      • homozygotes exhibit profound insulin resistance in both skeletal muscle and liver   (MGI Ref ID J:46134)
      • insulin resistant compared to wild-type   (MGI Ref ID J:135659)
  • abnormal lipid homeostasis
    • dyslipidemia   (MGI Ref ID J:96047)
  • 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)
    • 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)
  • abnormal pancreatic beta cell morphology
    • individual beta cell size is decreased   (MGI Ref ID J:96047)
    • 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)
      • 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 beta cell proliferation and increased beta cell accounts for reduction in beta cell mass   (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)
  • 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)
  • 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 phenotype
  • decreased birth body size
    • homozygous neonates are 10% smaller than heterozygous or wild-type littermates   (MGI Ref ID J:46134)
  • decreased body weight
    • homozygotes exhibit a small reduction in body weight that persists during weaning and into adulthood   (MGI Ref ID J:46134)
    • at 5 weeks, male homozygotes weigh ~18% less than wild-type males   (MGI Ref ID J:74303)
    • weight loss
      • mice gained weight until about 9 weeks, and began to decline   (MGI Ref ID J:135659)
  • increased total body fat amount
    • female homozygotes store twice as much body fat as age-matched wild-type females   (MGI Ref ID J:64791)
  • obese
    • female homozygotes weigh 20% more than wild-type females and are obese despite elevated leptin levels   (MGI Ref ID J:64791)
  • 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)
    • decreased oocyte number
      • at E18.5, mutant ovaries contain decreased numbers of primary oocytes relative to wild-type ovaries   (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)
    • 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)
  • abnormal ovulation
    • female homozygotes are resistant to exogenous gonadotropin stimulation   (MGI Ref ID J:64791)
    • however, uterine tissues of mutant females respond normally to exogenous sex steroids   (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)
  • 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)
  • female infertility
    • when bred with homozygous mutant males, 0% of homozygous virgin females become pregnant during an 8-week period   (MGI Ref ID J:64791)
    • 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)
  • 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)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Irs2tm1Mfw related

Diabetes and Obesity Research
Insulin Receptors and Growth Factors
Type 2 Diabetes (NIDDM)

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Irs2tm1Mfw
Allele Name targeted mutation 1, Morris F White
Allele Type Targeted (Null/Knockout)
Common Name(s) Irs2-;
Mutation Made By Morris White,   Joslin Diabetes Center/HHMI
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line NameR1
ES Cell Line Strain(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name Irs2, insulin receptor substrate 2
Chromosome 8
Gene Common Name(s) 4PS; IRS-2;
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. [MGI Ref ID J:46134]

Genotyping

Genotyping Information

Genotyping Protocols

Irs2tm1Mfw, Separated PCR
Irs2tm1Mfw, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

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: 9495343]  [MGI Ref ID J:46134]

Additional References

Irs2tm1Mfw related

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: 22210743]  [MGI Ref ID 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: 11014193]  [MGI Ref ID 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: 20604929]  [MGI Ref ID 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: 22288475]  [MGI Ref ID 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: 20959116]  [MGI Ref ID 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: 18802016]  [MGI Ref ID 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: 20028942]  [MGI Ref ID J:164152]

Griffeth RJ; Carretero J; Burks DJ. 2013. Insulin receptor substrate 2 is required for testicular development. PLoS One 8(5):e62103. [PubMed: 23741292]  [MGI Ref ID 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: 14617753]  [MGI Ref ID 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: 11812758]  [MGI Ref ID 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: 23478411]  [MGI Ref ID 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: 10642598]  [MGI Ref ID 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: 19523444]  [MGI Ref ID 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: 17299086]  [MGI Ref ID 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: 12488434]  [MGI Ref ID 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: 16154098]  [MGI Ref ID 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: 14693698]  [MGI Ref ID 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: 16170201]  [MGI Ref ID 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: 11994408]  [MGI Ref ID 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: 21955917]  [MGI Ref ID J:185333]

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: 12219087]  [MGI Ref ID 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: 24253047]  [MGI Ref ID J:208382]

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: 23560040]  [MGI Ref ID 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: 21926467]  [MGI Ref ID 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: 15705592]  [MGI Ref ID J:107134]

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: 12904469]  [MGI Ref ID 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: 17928362]  [MGI Ref ID 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: 16750510]  [MGI Ref ID J:110785]

Swindell WR. 2009. Accelerated failure time models provide a useful statistical framework for aging research. Exp Gerontol 44(3):190-200. [PubMed: 19007875]  [MGI Ref ID 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: 19095950]  [MGI Ref ID 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: 18288891]  [MGI Ref ID 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: 15685168]  [MGI Ref ID J:96047]

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: 10471495]  [MGI Ref ID 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: 20947509]  [MGI Ref ID 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: 15689562]  [MGI Ref ID J:98107]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryMice bearing the Irs2tm1Mfw allele were crossed to B6;129-Stat6tm1Gru targeted mutant mice in the laboratory of Dr. Michael Grusby, Harvard School of Public Health, Boston. The double mutant mice were kindly donated to The Jackson Laboratory. The Stat6tm1Gru allele was bred out of the stock which is currently maintained by breeding heterozygotes. Note that homozygotes are sterile.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.


See Terms of Use tab for General Terms and Conditions


The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
Ordering Information
JAX® Mice
Surgical and Preconditioning Services
JAX® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use


General Terms and Conditions


For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:207-288-6470

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.


(6.8)