Description

Strain Information

Former Names C57BL/6J-Ins2Akita    (Changed: 23-JUN-06 ) MODY    (Changed: 15-DEC-04 ) Type Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Inbred x Heterozygote         (Female x Male) TJL Breeding Summary: C57BL/6J female x Heterozygous male. Species laboratory mouse H2 Haplotype b Generation N26 (23-JAN-08)

Appearance
black
Related Genotype: a/a

Description
Mice heterozygous for the Akita spontaneous mutation (Ins2^Akita) are viable and fertile. Symptoms in heterozygous mutant mice include hyperglycemia, hypoinsulinemia, polydipsia, and polyuria, beginning around 3-4 weeks of age. The diabetic phenotype is more severe and progressive in the male than in the female. Obesity or insulitis does not accompany diabetes. Aged mice exhibit gait disturbance and decreased sensory nerve conduction velocity, but do not exhibit learning or memory deficits (Choeiri C et al., 2005). Progressive retinal abnormalities begin as early as 12 weeks after the onset of hyperglycemia. Retinal complications include increased vascular permeability, alterations in the morphology of astrocytes and microglia, increased apoptosis and thining of the inner layers of the retina. (Barber AJ, et al., 2005) The mean lifespan of diabetic male mice on the C57BL/NJcl background (305 days) was significantly shorter than that of nondiabetic males in another colony of the same strain (690 days). Mortality rates of diabetic and nondiabetic female mice of this strain did not differ significantly. Islets from Ins2^Akita mice are depleted of beta cells and those remaining release very little mature insulin. This, and the finding that mutant mice respond to exogenously administered insulin, indicate that Ins2^Akita mice will serve as an excellent substitute for mice made insulin dependent diabetic by treatment with alloxan or streptozotocin. Heterozygous Ins2^Akita mice are also ideally suited to allogeneic or xenogeneic islet transplantation protocols because the investigator does not need to treat the mice with a diabe togen to induce the hyperglycemic state. Untreated homozygotes rarely survive beyond 12 weeks of age.

Development
The founder mouse, a female, was discovered in the laboratory of Dr. Akio Koizumi among C57BL/6NSlc mice purchased from Shizuoka Japan (lab code Slc), and was bred to a C57BL/6NJcl male from Clea Japan, Inc. (lab code Jcl). Diabetic male progeny were backcrossed to C57BL/6NJcl females for 7+generations (According to Dr. Koizumi, the Wang et al. reference is mistaken in identifying the strain background as C57BL/6J) prior to importing into The Jackson Laboratory. At the Jackson Laboratory they have been backcrossed onto the C57BL/6J background and reached N13 in May 2003. The gene/mutation, originally called Mody4, was later identified as a mutation at the Ins2 locus and renamed Ins2^Akita.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Ins2^Akita allele

006860	B6.129-Ins2Akita Bdkrb2tm1Jfh/SmiJ
006580	B6.Cg-Ins2Akita Ldlrtm1Her/J
004369	B6.Cg-Rag1tm1Mom Ins2Akita/J
007562	D2.B6-Ins2Akita/MatbJ
006867	FVB.B6-Ins2Akita/MlnJ

View Strains carrying   Ins2^Akita     (5 strains)

Strains carrying other alleles of Ins2

005739	NOD-Tg(H2-Ea-Ins2)1Wehi/WehiJ
005036	NOD.129S2(B6)-Ins2tm1Jja/GseJ
005524	NOD.Cg-Tg(Ins2*Y16A)1Ell Ins1tm1Jja Ins2tm1Jja/GseJ
005525	NOD.Cg-Tg(Ins2*Y16A)3Ell Ins1tm1Jja Ins2tm1Jja/GseJ

View Strains carrying other alleles of Ins2     (4 strains)

Additional Web Information

Genetic Quality Control Annual Report
JAX Communication No. 5

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

	Diabetes Mellitus, Insulin-Dependent, 2 - Models with phenotypic similarity to human disease where etiologies are distinct.2
	Diabetes Mellitus, Permanent Neonatal; PNDM - Models with phenotypic similarity to human disease where etiologies are distinct.2
	Maturity-Onset Diabetes of the Young; MODY - Models with phenotypic similarity to human disease where etiologies are distinct.2

2 Human genes are associated with this disease. Orthologs of those genes do not appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Ins2^Akita/Ins2⁺

        C57BL/6-Ins2^Akita

• life span-post-weaning/aging
• premature death (MGI Ref ID J:40063)
  • 50% survival time in males is reduced to 305 days but survival time is not reduced for females through 370 days of age
  • mice have much shorter lifespan than wild-type; 909 days (wt) vs 373 days (mutant)
• homeostasis/metabolism phenotype
• decreased circulating insulin level (MGI Ref ID J:40063)
  • insulin levels are decreased in the blood and pancreas
• hyperglycemia (MGI Ref ID J:40063)
  • develops soon after weaning and is more severe in males
  • blood glucose in fed 7-8 week old males measures 544+/-11 mg/dl
• impaired glucose tolerance (MGI Ref ID J:40063)
• endocrine/exocrine gland phenotype
• abnormal Leydig cell morphology (MGI Ref ID J:108948)
  • mutant males display some pigmented vacuoles in Leydig cells in the testes, but to a lesser extent than in double mutant males at 12 months of age
• abnormal pancreatic beta cell morphology (MGI Ref ID J:47883)
  • density of beta cells is decreased at 14 days of age
  • beta cells have increased amounts of endoplasmic reticulum and Golgi complexes, more and enlarged mitochondria, and partial degranulation
• decreased insulin secretion (MGI Ref ID J:40063)
  • hyposecretion of insulin is seen; however, islet area is not reduced
  • the pancreatic ratio of insulin to glucagon is decreased to 0.42 and 0.54 at birth and 14 days of age, respectively compared to 1.17 and 1.11 in wild-type mice
• renal/urinary system phenotype
• hydronephrosis (MGI Ref ID J:40063)
  • seen in all diabetic males but only 5 of 20 diabetic females
• polyuria (MGI Ref ID J:40063)
  • develops soon after weaning and is more severe in males
• behavior/neurological phenotype
• hypoactivity (MGI Ref ID J:125256)
  • 7-8 week old males exhibit decreased locomotor activity as measured in open field test
  • number of total entries in elevated plus maze is decreased in 7-8 week old males as compared to controls
• increased anxiety-related response (MGI Ref ID J:125256)
  • 7-8 week old males exhibit greater anxiety behavior in elevated plus maze
  • total number and total time of entries in the open arms is significantly decreased as compared to controls
• increased drinking behavior (MGI Ref ID J:125256)
  • 7-8 week old males consume 7 fold more water as compared to controls (33.28 ml/day v. 4.68 ml/day)
• polydipsia (MGI Ref ID J:40063)
  • develops soon after weaning and is more severe in males
• no spontaneous movement (MGI Ref ID J:125256)
  • 7-8 week old males exhibit increased immobility time as measured in open field test
• polyphagia (MGI Ref ID J:125256)
  • 7-8 week old males consume 2 fold more food as compared to controls (8.16 g/day v. 4.48 g/day)
• growth/size phenotype
• decreased body weight (MGI Ref ID J:125256)
  • 7-8 week old males exhibit decreased weight as compared to controls (24g v. 26g)
• postnatal growth retardation (MGI Ref ID J:40063)
  • weight gain is normal through 18 weeks of age but then no further weight gain is seen and by 30 weeks weight loss is observed
• digestive/alimentary phenotype
• abnormal pancreatic beta cell morphology (MGI Ref ID J:47883)
  • density of beta cells is decreased at 14 days of age
  • beta cells have increased amounts of endoplasmic reticulum and Golgi complexes, more and enlarged mitochondria, and partial degranulation
• decreased insulin secretion (MGI Ref ID J:40063)
  • hyposecretion of insulin is seen; however, islet area is not reduced
  • the pancreatic ratio of insulin to glucagon is decreased to 0.42 and 0.54 at birth and 14 days of age, respectively compared to 1.17 and 1.11 in wild-type mice
• adipose tissue phenotype
• decreased subcutaneous adipose tissue amount (MGI Ref ID J:108948)
  • mutants have almost no subcutaneous fat
• cellular phenotype
• abnormal mitochondrial physiology (MGI Ref ID J:108948)
  • mutant mice show greater mitochondrial damage than wild-type or Bdkrb2-deficient mice at 12 months of age
• reproductive system phenotype
• abnormal Leydig cell morphology (MGI Ref ID J:108948)
  • mutant males display some pigmented vacuoles in Leydig cells in the testes, but to a lesser extent than in double mutant males at 12 months of age
• skeleton phenotype
• decreased bone density (MGI Ref ID J:108948)
  • mutants have significantly reduced bone density compared to wild-type or Bdkrb2-deficient mice
• kyphosis (MGI Ref ID J:108948)
  • diabetic mice display kyphosis but to a lesser extent than double mutant mice

Ins2^Akita/Ins2⁺

        C57BL/6-Ins2^Akita/J

• homeostasis/metabolism phenotype
• hyperglycemia (MGI Ref ID J:99412)
  • heterozygous males and females are hyperglycemic by 6 weeks of age (plasma glucose - 325 mg/dL); at 12 and 18 weeks of age, plasma glucose levels in males have appproximately doubled (645 mg/dL and 666 mg/dL) while levels in female mutants have increased much less (341 and 298 mg/dL respectively)
• increased insulin sensitivity (MGI Ref ID J:76224)
  • diabetic males that are hyperglycemic (plasma glucose - ~660 mg/dL) at 12 weeks show a return to euglycemia one hour after receiving 1 unit of insulin, demonstrating insulin sensitivity
• immune system phenotype
• abnormal microglial cell morphology (MGI Ref ID J:99412)
  • after 31-36 weeks of hyperglycemia, retinal microglia have a reactive morphology
• abnormal response to transplant (MGI Ref ID J:76224)
  • hyperglycemic male mice transplanted with pancreatic islets from wild-type B6 males become euglycemic in one week after transplant and remain euglycemic until removal of the graft (8 weeks); male mice receiving an allogeneic transplant of BALB/c wild-type islets initially become euglycemic but revert to hyperglycemia because of rejection of the graft
• increased leukocyte cell number (MGI Ref ID J:99412)
  • after 31-36 weeks of hyperglycemia, the number of leukocytes per retina is increased
• cardiovascular system phenotype
• abnormal retinal vasculature (MGI Ref ID J:99412)
  • after 31-36 weeks of hyperglycemia, a modest increase in the number of acellular capillaries is seen in the retina
• increased vascular permeability (MGI Ref ID J:99412)
  • vascular permeability is increased in the retina
• growth/size phenotype
• decreased body weight (MGI Ref ID J:99412)
  • at death heterozygous males weigh significantly less than wild-type males
• nervous system phenotype
• abnormal astrocyte morphology (MGI Ref ID J:99412)
  • after 31-36 weeks of hyperglycemia, astrocytes close to large caliber superficial blood vessels in the retina have short projections that do not conjoin with the vessel
• abnormal microglial cell morphology (MGI Ref ID J:99412)
  • after 31-36 weeks of hyperglycemia, retinal microglia have a reactive morphology
• vision/eye phenotype
• abnormal retinal apoptosis (MGI Ref ID J:99412)
  • after 31-36 weeks of hyperglycemia, significantly more caspase-3 positive cells are seen
• abnormal retinal neuronal layer morphology (MGI Ref ID J:99412)
  • after 22 weeks of hyperglycemia, in the peripheral regions the inner nuclear layer and inner plexiform layer thickness are reduced by 15.6% and 27%, respectively, and in the central region the thickness of the inner plexiform layer is reduced by 16.7%
• abnormal retinal ganglion layer morphology (MGI Ref ID J:99412)
  • after 22 weeks of hyperglycemia, the number of nuclei in the retinal ganglion cell layer is reduced by 23.4%
• abnormal retinal vasculature (MGI Ref ID J:99412)
  • after 31-36 weeks of hyperglycemia, a modest increase in the number of acellular capillaries is seen in the retina
• hematopoietic system phenotype
• abnormal microglial cell morphology (MGI Ref ID J:99412)
  • after 31-36 weeks of hyperglycemia, retinal microglia have a reactive morphology
• increased leukocyte cell number (MGI Ref ID J:99412)
  • after 31-36 weeks of hyperglycemia, the number of leukocytes per retina is increased

Ins2^Akita/Ins2^Akita

        C57BL/6-Ins2^Akita

• lethality-postnatal
• postnatal lethality (MGI Ref ID J:47883)
• homeostasis/metabolism phenotype
• hyperglycemia (MGI Ref ID J:47883)
  • blood glucose levels are slightly higher at 1 day of age and much higher at 14 days of age with no gender differences seen
• endocrine/exocrine gland phenotype
• abnormal islet of Langerhans morphology (MGI Ref ID J:47883)
  • islet area is reduced
• abnormal pancreatic alpha cell morphology (MGI Ref ID J:47883)
  • alpha cell density is markedly increased
• abnormal pancreatic beta cell morphology (MGI Ref ID J:47883)
  • density of beta cells is decreased within 24 hours of birth and at 2 weeks of age
  • beta cell granules are fewer in number and smaller and mitochondrial swelling and an increase in endoplasmic reticulum are seen at 2 weeks of age
• decreased insulin secretion (MGI Ref ID J:47883)
  • the pancreatic ratio of insulin to glucagon is decreased to 0.21 and 0.01 at birth and 14 days of age, respectively, compared to 1.17 and 1.11 in wild-type mice
• digestive/alimentary phenotype
• abnormal islet of Langerhans morphology (MGI Ref ID J:47883)
  • islet area is reduced
• abnormal pancreatic alpha cell morphology (MGI Ref ID J:47883)
  • alpha cell density is markedly increased
• abnormal pancreatic beta cell morphology (MGI Ref ID J:47883)
  • density of beta cells is decreased within 24 hours of birth and at 2 weeks of age
  • beta cell granules are fewer in number and smaller and mitochondrial swelling and an increase in endoplasmic reticulum are seen at 2 weeks of age
• decreased insulin secretion (MGI Ref ID J:47883)
  • the pancreatic ratio of insulin to glucagon is decreased to 0.21 and 0.01 at birth and 14 days of age, respectively, compared to 1.17 and 1.11 in wild-type mice

Ins2^Akita/Ins2^Akita

        C57BL/6-Ins2^Akita/J

• life span-post-weaning/aging
• premature death (MGI Ref ID J:76224)
  • untreated homozygous mice rarely survive past 12 weeks of age, with death resulting from extreme hyperglycemia;
• homeostasis/metabolism phenotype
• hyperglycemia (MGI Ref ID J:76224)
  • homozygous mice rapidly become hyperglycemic

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Ins2^Akita/Ins2⁺

        involves: C3H * C57BL/6NJcl * C57BL/6NSlc

• homeostasis/metabolism phenotype
• hyperglycemia (MGI Ref ID J:40063)
  • progressive increase in morning blood glucose level is seen
• impaired glucose tolerance (MGI Ref ID J:40063)

View Research Applications

Research Applications

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

Ins2 related

Diabetes and Obesity Research
Type 1 Diabetes (IDDM) Analysis Strains (NOD/ShiLtJ Non-MHC Congenics)

Immunology and Inflammation Research
Autoimmunity (Type 1 Diabetes)

Ins2^Akita related

Cell Biology Research
Protein Processing

Diabetes and Obesity Research
Hyperglycemia
Hypoinsulinemia
Impaired Insulin Processing
Insulin Receptors and Growth Factors
Islet Transplantation Studies
Type 1 Diabetes (IDDM) (MODY, mature onset diabetes of the young)

Endocrine Deficiency Research
Pancreas Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Ins2Akita
Allele Name		Akita
Allele Type		Spontaneous
Common Name(s)		Ins2C96Y; Ins2Mody; Mody; Mody4;
Strain of Origin		C57BL/6
Gene Symbol and Name		Ins2, insulin II
Chromosome		7
Gene Common Name(s)		AA986540; ILPR; IRDN; Ins-2; InsII; Mody; Mody4; expressed sequence AA986540; maturity onset diabetes of the young; maturity onset diabetes of the young 4;
Molecular Note		In the mutant allele a transition from G to A at nucleotide 1907 disrupted an Fnu4HI site in exon 3. This mutation changed the seventh amino acid in the A chain of mature insulin, Cys96 (TGC), to Tyr (TAC). The authors predict that the transition would disrupt a disulfide bond between the A and the B chains and would likely induce a major conformational change in insulin 2 molecules. RT-PCR studies suggest that both normal and mutant Ins2 alleles are transcribed similarly in pancreatic islets of heterozygous mice, although immunofluorescence and immunoblot analyses of heterozygous islets detected reduced levels of insulin and proinsulin. [MGI Ref ID J:51935]

Genotyping

Genotyping Information

Genotyping Protocols

Ins2^Akita, PYRO, vers. 2
Ins2^Akita, REST, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Fujita H; Haseyama T; Kayo T; Nozaki J; Wada Y; Ito S; Koizumi A. 2001. Increased expression of glutathione S-transferase in renal proximal tubules in the early stages of diabetes: a study of type-2 diabetes in the Akita mouse model. Exp Nephrol 9(6):380-6. [PubMed: 11701997]  [MGI Ref ID J:109862]

Kayo T; Koizumi A. 1998. Mapping of murine diabetogenic gene mody on chromosome 7 at D7Mit258 and its involvement in pancreatic islet and beta cell development during the perinatal period. J Clin Invest 101(10):2112-8. [PubMed: 9593767]  [MGI Ref ID J:47883]

Mathews CE; Langley SH; Leiter EH. 2002. New mouse model to study islet transplantation in insulin-dependent diabetes mellitus. Transplantation 73(8):1333-6. [PubMed: 11981430]  [MGI Ref ID J:76224]

Oyadomari S; Koizumi A; Takeda K; Gotoh T; Akira S; Araki E; Mori M. 2002. Targeted disruption of the Chop gene delays endoplasmic reticulum stress-mediated diabetes. J Clin Invest 109(4):525-32. [PubMed: 11854325]  [MGI Ref ID J:74700]

Ron D. 2002. Proteotoxicity in the endoplasmic reticulum: lessons from the Akita diabetic mouse. J Clin Invest 109(4):443-5. [PubMed: 11854314]  [MGI Ref ID J:78863]

Wang J; Takeuchi T; Tanaka S; Kubo SK; Kayo T; Lu D; Takata K; Koizumi A; Izumi T. 1999. A mutation in the insulin 2 gene induces diabetes with severe pancreatic beta-cell dysfunction in the Mody mouse. J Clin Invest 103(1):27-37. [PubMed: 9884331]  [MGI Ref ID J:51935]

Yoshioka M; Kayo T; Ikeda T; Koizumi A. 1997. A novel locus, Mody4, distal to D7Mit189 on chromosome 7 determines early-onset NIDDM in nonobese C57BL/6 (Akita) mutant mice. Diabetes 46(5):887-94. [PubMed: 9133560]  [MGI Ref ID J:40063]

Additional References

Ins2^Akita related

Asakawa A; Toyoshima M; Inoue K; Koizumi A. 2007. Ins2Akita mice exhibit hyperphagia and anxiety behavior via the melanocortin system. Int J Mol Med 19(4):649-52. [PubMed: 17334640]  [MGI Ref ID J:125256]

Barber AJ; Antonetti DA; Kern TS; Reiter CE; Soans RS; Krady JK; Levison SW; Gardner TW; Bronson SK. 2005. The Ins2Akita mouse as a model of early retinal complications in diabetes. Invest Ophthalmol Vis Sci 46(6):2210-8. [PubMed: 15914643]  [MGI Ref ID J:99412]

Chang AS; Dale AN; Moley KH. 2005. Maternal diabetes adversely affects preovulatory oocyte maturation, development, and granulosa cell apoptosis. Endocrinology 146(5):2445-53. [PubMed: 15718275]  [MGI Ref ID J:129826]

Choeiri C; Hewitt K; Durkin J; Simard CJ; Renaud JM; Messier C. 2005. Longitudinal evaluation of memory performance and peripheral neuropathy in the Ins2(C96Y) Akita mice. Behav Brain Res 157(1):31-8. [PubMed: 15617768]  [MGI Ref ID J:95284]

Gastinger MJ; Kunselman AR; Conboy EE; Bronson SK; Barber AJ. 2008. Dendrite remodeling and other abnormalities in the retinal ganglion cells of Ins2 Akita diabetic mice. Invest Ophthalmol Vis Sci 49(6):2635-42. [PubMed: 18515593]  [MGI Ref ID J:137045]

Gastinger MJ; Singh RS; Barber AJ. 2006. Loss of cholinergic and dopaminergic amacrine cells in streptozotocin-diabetic rat and Ins2Akita-diabetic mouse retinas. Invest Ophthalmol Vis Sci 47(7):3143-50. [PubMed: 16799061]  [MGI Ref ID J:112243]

Gurley SB; Clare SE; Snow KP; Hu A; Meyer TW; Coffman TM. 2006. Impact of genetic background on nephropathy in diabetic mice. Am J Physiol Renal Physiol 290(1):F214-22. [PubMed: 16118394]  [MGI Ref ID J:104083]

Gyurko R; Siqueira CC; Caldon N; Gao L; Kantarci A; Van Dyke TE. 2006. Chronic hyperglycemia predisposes to exaggerated inflammatory response and leukocyte dysfunction in Akita mice. J Immunol 177(10):7250-6. [PubMed: 17082643]  [MGI Ref ID J:140617]

Haseyama T; Fujita T; Hirasawa F; Tsukada M; Wakui H; Komatsuda A; Ohtani H; Miura AB; Imai H; Koizumi A. 2002. Complications of IgA nephropathy in a non-insulin-dependent diabetes model, the Akita mouse. Tohoku J Exp Med 198(4):233-44. [PubMed: 12630555]  [MGI Ref ID J:107880]

Hirosawa M; Minata M; Harada KH; Hitomi T; Krust A; Koizumi A. 2008. Ablation of estrogen receptor alpha (ERalpha) prevents upregulation of POMC by leptin and insulin. Biochem Biophys Res Commun 371(2):320-3. [PubMed: 18439911]  [MGI Ref ID J:136249]

Hong EG; Jung DY; Ko HJ; Zhang Z; Ma Z; Jun JY; Kim JH; Sumner AD; Vary TC; Gardner TW; Bronson SK; Kim JK. 2007. Nonobese, insulin-deficient Ins2Akita mice develop type 2 diabetes phenotypes including insulin resistance and cardiac remodeling. Am J Physiol Endocrinol Metab 293(6):E1687-96. [PubMed: 17911348]  [MGI Ref ID J:130021]

Iwakura H; Akamizu T; Ariyasu H; Irako T; Hosoda K; Nakao K; Kangawa K. 2007. Effects of ghrelin administration on decreased growth hormone status in obese animals. Am J Physiol Endocrinol Metab 293(3):E819-25. [PubMed: 17595213]  [MGI Ref ID J:125421]

Izumi T; Yokota-Hashimoto H; Zhao S; Wang J; Halban PA; Takeuchi T. 2003. Dominant negative pathogenesis by mutant proinsulin in the Akita diabetic mouse. Diabetes 52(2):409-16. [PubMed: 12540615]  [MGI Ref ID J:107156]

Kakoki M; Kizer CM; Yi X; Takahashi N; Kim HS; Bagnell CR; Edgell CJ; Maeda N; Jennette JC; Smithies O. 2006. Senescence-associated phenotypes in Akita diabetic mice are enhanced by absence of bradykinin B2 receptors. J Clin Invest 116(5):1302-9. [PubMed: 16604193]  [MGI Ref ID J:108948]

Kakoki M; Takahashi N; Jennette JC; Smithies O. 2004. Diabetic nephropathy is markedly enhanced in mice lacking the bradykinin B2 receptor. Proc Natl Acad Sci U S A 101(36):13302-5. [PubMed: 15326315]  [MGI Ref ID J:92403]

Liu Z; Tanabe K; Bernal-Mizrachi E; Permutt MA. 2008. Mice with beta cell overexpression of glycogen synthase kinase-3beta have reduced beta cell mass and proliferation. Diabetologia 51(4):623-31. [PubMed: 18219478]  [MGI Ref ID J:137936]

Lu YC; Sternini C; Rozengurt E; Zhukova E. 2005. Release of transgenic human insulin from gastric g cells: a novel approach for the amelioration of diabetes. Endocrinology 146(6):2610-9. [PubMed: 15731364]  [MGI Ref ID J:99270]

Lu Z; Jiang YP; Xu XH; Ballou LM; Cohen IS; Lin RZ. 2007. Decreased L-type Ca2+ current in cardiac myocytes of type 1 diabetic Akita mice due to reduced phosphatidylinositol 3-kinase signaling. Diabetes 56(11):2780-9. [PubMed: 17666471]  [MGI Ref ID J:126727]

Nasrallah R; Xiong H; Hebert RL. 2007. Renal prostaglandin E2 receptor (EP) expression profile is altered in streptozotocin and B6-Ins2Akita type I diabetic mice. Am J Physiol Renal Physiol 292(1):F278-84. [PubMed: 16954344]  [MGI Ref ID J:118086]

Nozaki J; Kubota H; Yoshida H; Naitoh M; Goji J; Yoshinaga T; Mori K; Koizumi A; Nagata K. 2004. The endoplasmic reticulum stress response is stimulated through the continuous activation of transcription factors ATF6 and XBP1 in Ins2+/Akita pancreatic beta cells. Genes Cells 9(3):261-70. [PubMed: 15005713]  [MGI Ref ID J:96748]

Oyadomari S; Yun C; Fisher EA; Kreglinger N; Kreibich G; Oyadomari M; Harding HP; Goodman AG; Harant H; Garrison JL; Taunton J; Katze MG; Ron D. 2006. Cotranslocational degradation protects the stressed endoplasmic reticulum from protein overload. Cell 126(4):727-39. [PubMed: 16923392]  [MGI Ref ID J:115988]

Pearson T; Shultz LD; Lief J; Burzenski L; Gott B; Chase T; Foreman O; Rossini AA; Bottino R; Trucco M; Greiner DL. 2008. A new immunodeficient hyperglycaemic mouse model based on the Ins2 ( Akita ) mutation for analyses of human islet and beta stem and progenitor cell function. Diabetologia 51(8):1449-56. [PubMed: 18563383]  [MGI Ref ID J:138005]

Proctor G; Jiang T; Iwahashi M; Wang Z; Li J; Levi M. 2006. Regulation of renal fatty acid and cholesterol metabolism, inflammation, and fibrosis in Akita and OVE26 mice with type 1 diabetes. Diabetes 55(9):2502-9. [PubMed: 16936198]  [MGI Ref ID J:116591]

Takeshita S; Moritani M; Kunika K; Inoue H; Itakura M. 2006. Diabetic modifier QTLs identified in F2 intercrosses between Akita and A/J mice. Mamm Genome 17(9):927-40. [PubMed: 16964447]  [MGI Ref ID J:112869]

Tchekneva EE; Rinchik EM; Polosukhina D; Davis LS; Kadkina V; Mohamed Y; Dunn SR; Sharma K; Qi Z; Fogo AB; Breyer MD. 2007. A sensitized screen of N-ethyl-N-nitrosourea-mutagenized mice identifies dominant mutants predisposed to diabetic nephropathy. J Am Soc Nephrol 18(1):103-12. [PubMed: 17151334]  [MGI Ref ID J:135943]

Wong DW; Oudit GY; Reich H; Kassiri Z; Zhou J; Liu QC; Backx PH; Penninger JM; Herzenberg AM; Scholey JW. 2007. Loss of angiotensin-converting enzyme-2 (Ace2) accelerates diabetic kidney injury. Am J Pathol 171(2):438-51. [PubMed: 17600118]  [MGI Ref ID J:123932]

Yamaguchi S; Ishihara H; Yamada T; Tamura A; Usui M; Tominaga R; Munakata Y; Satake C; Katagiri H; Tashiro F; Aburatani H; Tsukiyama-Kohara K; Miyazaki J; Sonenberg N; Oka Y. 2008. ATF4-mediated induction of 4E-BP1 contributes to pancreatic beta cell survival under endoplasmic reticulum stress. Cell Metab 7(3):269-76. [PubMed: 18316032]  [MGI Ref ID J:133217]

Zuber C; Fan JY; Guhl B; Roth J. 2004. Misfolded proinsulin accumulates in expanded pre-Golgi intermediates and endoplasmic reticulum subdomains in pancreatic beta cells of Akita mice. FASEB J 18(7):917-9. [PubMed: 15033933]  [MGI Ref ID J:118471]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB29

Colony Maintenance

Breeding & Husbandry	Mice are currently maintained by breeding a C57BL/6J inbred female with a heterozygous male. After onset of diabetes, when cages become very wet (due to diabetes- associated polyuria), the health of heterozygotes is best maintained by housing them individually in cages containing a mixture of regular litter and Alpha-Dri, changed twice weekly.
Mating System	Inbred x Heterozygote         (Female x Male)
	TJL Breeding Summary: C57BL/6J female x Heterozygous male.
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Mouse Mutant Resource collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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.

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Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, 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 The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials 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 The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.