Strain Name:

FVB.B6-Ins2Akita/MlnJ

Stock Number:

006867

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Availability:

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Whereas untreated FVB/NJ mice homozygous for the Akita spontaneous mutation of the insulin 2 gene (Ins2Akita) rarely survive beyond 12 weeks of age, heterozygotes are viable and fertile. Hyperglycemia, hypoinsulinemia, polydipsia, and polyuria, are more severe than in C57BL/6-Ins2Akita/J (Stock No.003548) mutants. Obesity and insulitis do not accompany diabetes. Hyperglycemia in females becomes more severe during pregnancy and leading to embryo malformations and reabsorption, even with insulin therapy. This strain responds to exogenously administered insulin, and is an excellent substitute for mice made insulin-dependent diabetic with alloxan or streptozotocin. It is also ideally suited to allogeneic or xenogeneic islet transplantation.

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 Congenic; Mutant Strain; Spontaneous Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Specieslaboratory mouse
Background Strain FVB/N
Donor Strain C57BL/6J
H2 Haplotypeq
GenerationN9+N2pN1
Generation Definitions
 
Donating InvestigatorDr. Mary Loeken,   Joslin Diabetes Center

Appearance
albino
Related Genotype: A/A Tyrc/Tyrc

Description
FVB/NJ mice heterozygous for the Akita spontaneous mutation are viable and fertile. The donating investigator reports that the symptoms in heterozygous mutant mice are more severe than those observed in C57BL/6-Ins2Akita mice (Stock No. 003548). These symptoms include hyperglycemia (females > 600mg/dl, males ~560 mg/dl), hypoinsulinemia, polydipsia, and polyuria, beginning at approximately 3-4 weeks of age. In contrast to Akita heterozygotes on a C57BL/6 background, FVB/NJ adult heterozygous females are more hyperglycemic than heterozygous males. Obesity and insulitis do not accompany diabetes. Ins2 is expressed in the fetal yolk sac and is maternally imprinted. Heterozygous mutant females become more hyperglycemic during pregnancy, and are susceptible to embryo malformations leading to reabsorption, even with insulin therapy. Heterozygous mutant males do not produce mutant and wild-type offspring in Mendelian ratios. Litter sizes from crosses using either heterozygous males or females are reduced (5-8 pups/litter) compared to litters from control FVB/NJ mice (10 pups/litter).

Although not studied in this FVB/NJ genetic background background, heterozygous mutant mice on the C57BL/6 background 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 thinning 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 Akita heterozygous mice are depleted of beta cells, and the remaining beta cells release very little mature insulin. This, and the finding that mutant mice respond to exogenously administered insulin, indicates that Akita mice can serve as an excellent substitute for mice made insulin dependent diabetic by treatment with alloxan or streptozotocin. Heterozygous Akita mice also are ideally suited as hosts for allogeneic or xenogeneic islet transplantation protocols because treating the mice with a diabetogen is not required to induce the hyperglycemic state. Homozygotes untreated with insulin rarely survive beyond 12 weeks of age.

This strain may be useful as a model for insulin-dependent diabetes, and in studies involving diabetic embryopathy.

Development
Ins2Akita is a dominant, spontaneous, point mutation, that introduces a Cys to Tyr substitution at the seventh amino acid in the A chain of mature insulin (amino acid 96 in the preproinsulin II sequence), and results in a major conformational change in the insulin 2 molecule. The Ins2Akita spontaneous mutation on the C57BL/6 background (Stock No. 003548) was backcrossed to FVB/NJ for 9 generations. Speed congenic analysis confirmed the N6 generation was <0.2% C57BL/6J and the sex chromosomes were fixed at generations N6 and N7. In 2007, the Type 1 Diabetes Resource received this strain at N9 and mated it to FVB/NJ for 1 generation prior to initiating sibling matings.

Control Information

  Control
   Wild-type from the colony
   001800 FVB/NJ
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying   Ins2Akita     (10 strains)

View Strains carrying other alleles of Ins2     (7 strains)

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, Permanent Neonatal; PNDM
- Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).
Diabetes Mellitus, Insulin-Dependent; IDDM
Diabetes Mellitus, Noninsulin-Dependent; NIDDM
Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.
Maturity-Onset Diabetes of the Young; MODY
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Diabetes Mellitus, Insulin-Dependent, 2   (INS)
Insulin; INS   (INS)
Maturity-Onset Diabetes of the Young, Type 10; MODY10   (INS)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Ins2Akita/Ins2+

        C57BL/6-Ins2Akita
  • mortality/aging
  • premature death
    • 50% survival time in males is reduced to 305 days but survival time is not reduced for females through 370 days of age   (MGI Ref ID J:40063)
    • mice have much shorter lifespan than wild-type; 909 days (wt) vs 373 days (mutant)   (MGI Ref ID J:108948)
  • homeostasis/metabolism phenotype
  • decreased circulating insulin level
    • insulin levels are decreased in the blood and pancreas   (MGI Ref ID J:40063)
  • decreased insulin secretion
    • hyposecretion of insulin is seen; however, islet area is not reduced   (MGI Ref ID J:40063)
    • 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   (MGI Ref ID J:47883)
  • hyperglycemia
    • develops soon after weaning and is more severe in males   (MGI Ref ID J:40063)
    • blood glucose in fed 7-8 week old males measures 544+/-11 mg/dl   (MGI Ref ID J:125256)
  • impaired glucose tolerance   (MGI Ref ID J:40063)
  • endocrine/exocrine gland phenotype
  • abnormal Leydig cell morphology
    • 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   (MGI Ref ID J:108948)
  • abnormal pancreatic beta cell morphology
    • density of beta cells is decreased at 14 days of age   (MGI Ref ID J:47883)
    • beta cells have increased amounts of endoplasmic reticulum and Golgi complexes, more and enlarged mitochondria, and partial degranulation   (MGI Ref ID J:47883)
    • degranulated pancreatic beta cells
      • partial degranulation   (MGI Ref ID J:47883)
  • decreased insulin secretion
    • hyposecretion of insulin is seen; however, islet area is not reduced   (MGI Ref ID J:40063)
    • 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   (MGI Ref ID J:47883)
  • renal/urinary system phenotype
  • hydronephrosis
    • seen in all diabetic males but only 5 of 20 diabetic females   (MGI Ref ID J:40063)
  • polyuria
    • develops soon after weaning and is more severe in males   (MGI Ref ID J:40063)
  • behavior/neurological phenotype
  • akinesia
    • 7-8 week old males exhibit increased immobility time as measured in open field test   (MGI Ref ID J:125256)
  • hypoactivity
    • 7-8 week old males exhibit decreased locomotor activity as measured in open field test   (MGI Ref ID J:125256)
    • number of total entries in elevated plus maze is decreased in 7-8 week old males as compared to controls   (MGI Ref ID J:125256)
  • increased anxiety-related response
    • 7-8 week old males exhibit greater anxiety behavior in elevated plus maze   (MGI Ref ID J:125256)
    • total number and total time of entries in the open arms is significantly decreased as compared to controls   (MGI Ref ID J:125256)
  • increased fluid intake
    • 7-8 week old males consume 7 fold more water as compared to controls (33.28 ml/day v. 4.68 ml/day)   (MGI Ref ID J:125256)
    • polydipsia
      • develops soon after weaning and is more severe in males   (MGI Ref ID J:40063)
  • polyphagia
    • 7-8 week old males consume 2 fold more food as compared to controls (8.16 g/day v. 4.48 g/day)   (MGI Ref ID J:125256)
  • growth/size/body phenotype
  • decreased body weight
    • 7-8 week old males exhibit decreased weight as compared to controls (24g v. 26g)   (MGI Ref ID J:125256)
  • postnatal growth retardation
    • 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   (MGI Ref ID J:40063)
  • adipose tissue phenotype
  • decreased subcutaneous adipose tissue amount
    • mutants have almost no subcutaneous fat   (MGI Ref ID J:108948)
  • cellular phenotype
  • abnormal mitochondrion morphology
    • mutant mice show greater mitochondrial damage than wild-type or Bdkrb2-deficient mice at 12 months of age   (MGI Ref ID J:108948)
  • reproductive system phenotype
  • abnormal Leydig cell morphology
    • 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   (MGI Ref ID J:108948)
  • skeleton phenotype
  • decreased bone mineral density
    • mutants have significantly reduced bone density compared to wild-type or Bdkrb2-deficient mice   (MGI Ref ID J:108948)
  • kyphosis
    • diabetic mice display kyphosis but to a lesser extent than double mutant mice   (MGI Ref ID J:108948)
  • integument phenotype
  • decreased subcutaneous adipose tissue amount
    • mutants have almost no subcutaneous fat   (MGI Ref ID J:108948)

Ins2Akita/Ins2+

        involves: C3H * C57BL/6NJcl * C57BL/6NSlc
  • homeostasis/metabolism phenotype
  • hyperglycemia
    • progressive increase in morning blood glucose level is seen   (MGI Ref ID J:40063)
  • impaired glucose tolerance   (MGI Ref ID J:40063)

Ins2Akita/Ins2+

        C57BL/6-Ins2Akita/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)   (MGI Ref ID J:76224)
  • increased insulin sensitivity
    • 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   (MGI Ref ID J:76224)
  • immune system phenotype
  • abnormal microglial cell morphology
    • after 31-36 weeks of hyperglycemia, retinal microglia have a reactive morphology   (MGI Ref ID J:99412)
  • abnormal response to transplant
    • 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   (MGI Ref ID J:76224)
  • increased leukocyte cell number
    • after 31-36 weeks of hyperglycemia, the number of leukocytes per retina is increased   (MGI Ref ID J:99412)
  • cardiovascular system phenotype
  • abnormal retinal vasculature morphology
    • after 31-36 weeks of hyperglycemia, a modest increase in the number of acellular capillaries is seen in the retina   (MGI Ref ID J:99412)
  • increased vascular permeability
    • vascular permeability is increased in the retina   (MGI Ref ID J:99412)
  • growth/size/body phenotype
  • decreased body weight
    • at death heterozygous males weigh significantly less than wild-type males   (MGI Ref ID J:99412)
  • nervous system phenotype
  • abnormal astrocyte morphology
    • 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   (MGI Ref ID J:99412)
  • abnormal microglial cell morphology
    • after 31-36 weeks of hyperglycemia, retinal microglia have a reactive morphology   (MGI Ref ID J:99412)
  • vision/eye phenotype
  • abnormal retinal apoptosis
    • after 31-36 weeks of hyperglycemia, significantly more caspase-3 positive cells are seen   (MGI Ref ID J:99412)
  • abnormal retinal neuronal layer morphology
    • 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%   (MGI Ref ID J:99412)
    • abnormal retinal ganglion layer morphology
      • after 22 weeks of hyperglycemia, the number of nuclei in the retinal ganglion cell layer is reduced by 23.4%   (MGI Ref ID J:99412)
  • abnormal retinal vasculature morphology
    • after 31-36 weeks of hyperglycemia, a modest increase in the number of acellular capillaries is seen in the retina   (MGI Ref ID J:99412)
  • hematopoietic system phenotype
  • abnormal microglial cell morphology
    • after 31-36 weeks of hyperglycemia, retinal microglia have a reactive morphology   (MGI Ref ID J:99412)
  • increased leukocyte cell number
    • after 31-36 weeks of hyperglycemia, the number of leukocytes per retina is increased   (MGI Ref ID J:99412)
  • cellular phenotype
  • abnormal retinal apoptosis
    • after 31-36 weeks of hyperglycemia, significantly more caspase-3 positive cells are seen   (MGI Ref ID J:99412)

Ins2Akita/Ins2+

        C.B6N-Ins2Akita
  • homeostasis/metabolism phenotype
  • albuminuria
    • 3-fold increase in albumin-to-creatine ratio at 4 months of age, however albuminuria does not persist at 6 months of age   (MGI Ref ID J:198186)
  • renal/urinary system phenotype
  • albuminuria
    • 3-fold increase in albumin-to-creatine ratio at 4 months of age, however albuminuria does not persist at 6 months of age   (MGI Ref ID J:198186)
  • expanded mesangial matrix
    • mesangial matrix expansion is seen at 4 months of age   (MGI Ref ID J:198186)
  • glomerulosclerosis
    • same degree of glomerular injury as in homozygotes at 6 months of age   (MGI Ref ID J:198186)
  • increased renal glomerular filtration rate
    • glomerular filtration rate is increased at 6 months of age   (MGI Ref ID J:198186)

Ins2Akita/Ins2+

        involves: C57BL/6NSlc
  • homeostasis/metabolism phenotype
  • *normal* homeostasis/metabolism phenotype
    • mice exhibit normal insulin sensitivity   (MGI Ref ID J:200802)
    • decreased circulating leptin level   (MGI Ref ID J:200802)
    • decreased insulin secretion
      • decreased total pancreatic insulin and prolinsulin content   (MGI Ref ID J:200802)
    • increased circulating glucose level   (MGI Ref ID J:200802)
  • endocrine/exocrine gland phenotype
  • abnormal pancreatic islet morphology
    • beta cells contain a small number of secretory granules, a tubulovesicular structure comprised of enlarged endoplasmic reticulum, and swelling or disruption of mitochondria   (MGI Ref ID J:200802)
  • decreased insulin secretion
    • decreased total pancreatic insulin and prolinsulin content   (MGI Ref ID J:200802)
  • growth/size/body phenotype
  • decreased body weight   (MGI Ref ID J:200802)
  • behavior/neurological phenotype
  • increased food intake   (MGI Ref ID J:200802)

Ins2Akita/Ins2Akita

        C57BL/6-Ins2Akita
  • mortality/aging
  • postnatal lethality   (MGI Ref ID J:47883)
  • homeostasis/metabolism phenotype
  • decreased insulin secretion
    • 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   (MGI Ref ID J:47883)
  • hyperglycemia
    • blood glucose levels are slightly higher at 1 day of age and much higher at 14 days of age with no gender differences seen   (MGI Ref ID J:47883)
  • endocrine/exocrine gland phenotype
  • abnormal pancreatic alpha cell morphology
    • alpha cell density is markedly increased   (MGI Ref ID J:47883)
  • abnormal pancreatic beta cell morphology
    • density of beta cells is decreased within 24 hours of birth and at 2 weeks of age   (MGI Ref ID J:47883)
    • 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   (MGI Ref ID J:47883)
  • decreased insulin secretion
    • 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   (MGI Ref ID J:47883)
  • small pancreatic islets
    • islet area is reduced   (MGI Ref ID J:47883)

Ins2Akita/Ins2Akita

        C57BL/6-Ins2Akita/J
  • mortality/aging
  • premature death
    • untreated homozygous mice rarely survive past 12 weeks of age, with death resulting from extreme hyperglycemia;   (MGI Ref ID J:76224)
  • homeostasis/metabolism phenotype
  • hyperglycemia
    • homozygous mice rapidly become hyperglycemic   (MGI Ref ID J:76224)

Ins2Akita/Ins2Akita

        involves: C57BL/6NSlc
  • endocrine/exocrine gland phenotype
  • abnormal pancreas physiology
    • expression of a proliferation marker in the pancreas islet is decreased compared to in wild-type mice   (MGI Ref ID J:156725)
    • abnormal pancreatic islet cell apoptosis
      • expression of apoptosis markers in the pancreas islet is increased compared to in wild-type mice   (MGI Ref ID J:156725)
    • decreased insulin secretion
      • pancreas insulin levels are lower than in Cebpbtm1.1Maka homozygotes   (MGI Ref ID J:156725)
  • decreased pancreatic beta cell mass
    • in 50% of mice at 8 weeks   (MGI Ref ID J:156725)
  • homeostasis/metabolism phenotype
  • decreased circulating insulin level   (MGI Ref ID J:156725)
  • decreased insulin secretion
    • pancreas insulin levels are lower than in Cebpbtm1.1Maka homozygotes   (MGI Ref ID J:156725)
  • hyperglycemia   (MGI Ref ID J:156725)
  • cardiovascular system phenotype
  • hematoma
    • greater hematoma expansion induced by autologous blood injection in diabetic mice   (MGI Ref ID J:168556)
  • cellular phenotype
  • abnormal pancreatic islet cell apoptosis
    • expression of apoptosis markers in the pancreas islet is increased compared to in wild-type mice   (MGI Ref ID J:156725)

Ins2Akita/Ins2Akita

        C.B6N-Ins2Akita
  • mortality/aging
  • premature death
    • approximately 20% of mutants fail to thrive and are sacrificed at 6 months of age   (MGI Ref ID J:198186)
  • cardiovascular system phenotype
  • abnormal glomerular capillary morphology
    • mice show a decrease in CD31 positive structures in the glomeruli, indicating collapse of the glomerular tufts   (MGI Ref ID J:198186)
  • growth/size/body phenotype
  • decreased body weight
    • reduced body weight at 4 and 6 months of age   (MGI Ref ID J:198186)
  • homeostasis/metabolism phenotype
  • albuminuria
    • 3-fold increase in albumin-to-creatine ratio at 4 months of age; albuminuria persists in mutants at 6 months of age   (MGI Ref ID J:198186)
  • hyperglycemia   (MGI Ref ID J:198186)
  • renal/urinary system phenotype
  • abnormal kidney interstitium morphology
    • small increase in collagen I in the tubulointerstitial compartment of the kidney   (MGI Ref ID J:198186)
    • however, tubulointerstitial fibrosis is not observed   (MGI Ref ID J:198186)
  • abnormal renal glomerulus morphology
    • increase in glomerular collagen IV deposition at 6 months of age   (MGI Ref ID J:198186)
    • abnormal glomerular capillary morphology
      • mice show a decrease in CD31 positive structures in the glomeruli, indicating collapse of the glomerular tufts   (MGI Ref ID J:198186)
    • expanded mesangial matrix
      • mesangial matrix expansion is seen at 4 months of age and is more pronounced than in heterozygous mice   (MGI Ref ID J:198186)
    • glomerulosclerosis
      • same degree of glomerular injury as in heterozygotes at 6 months of age   (MGI Ref ID J:198186)
  • albuminuria
    • 3-fold increase in albumin-to-creatine ratio at 4 months of age; albuminuria persists in mutants at 6 months of age   (MGI Ref ID J:198186)
  • increased renal glomerular filtration rate
    • glomerular filtration rate is increased at 4 months of age but decreased by 6 months of age to normal levels   (MGI Ref ID J:198186)
  • increased renal glomerulus basement membrane thickness   (MGI Ref ID J:198186)

Ins2Akita/?

        involves: C57BL/6NSlc
  • growth/size/body phenotype
  • decreased body weight   (MGI Ref ID J:130021)
  • adipose tissue phenotype
  • abnormal adipocyte glucose uptake
    • insulin-stimulated glucose uptake in white adipose tissue is increased more than 3-fold during hyperinsulinemic-euglycemic clamps   (MGI Ref ID J:130021)
    • insulin-stimulated glucose uptake in brown adipose tissue is reduced during hyperinsulinemic-euglycemic clamps   (MGI Ref ID J:130021)
  • abnormal adipose tissue amount
    • whole body fat mass is reduced at 8 and 3 weeks of age, however whole body lean mass is no different from wild-type   (MGI Ref ID J:130021)
  • behavior/neurological phenotype
  • hypoactivity
    • mutants are less active during a 24 hour cycle   (MGI Ref ID J:130021)
  • increased food intake
    • daily food intake is increased twofold   (MGI Ref ID J:130021)
  • homeostasis/metabolism phenotype
  • abnormal glucose homeostasis
    • during hyperinsulinemic-euglycemic clamps, mutants show a 40% reduction in insulin-stimulated whole body glucose turnover   (MGI Ref ID J:130021)
    • basal hepatic glucose production is increased   (MGI Ref ID J:130021)
    • hepatic glucose production remains elevated during the insulin clamp unlike in wild-type mice which show a decrease   (MGI Ref ID J:130021)
    • during hyperinsulinemic-euglycemic clamps, insulin-stimulated whole body glycolysis and glycogen plus lipid synthesis are reduced by 40-50%   (MGI Ref ID J:130021)
    • decreased circulating insulin level
      • fed insulin levels are reduced   (MGI Ref ID J:130021)
    • hyperglycemia
      • mutants develop overnight-fasted hyperglycemia   (MGI Ref ID J:130021)
    • insulin resistance
      • nonobese mutants develop insulin resistance in skeletal muscle, liver, and brown adipose tissue, as indicated by an approximate 80% reduction in glucose infusion rate during hyperinsulinemic-euglycemic clamps   (MGI Ref ID J:130021)
      • chronic treatment with phloridzin to chronically lower circulating glucose levels normalizes peripheral insulin action but does not normalize hepatic insulin action   (MGI Ref ID J:130021)
  • decreased respiratory quotient
    • respiratory exchange ratio is reduced, indicating increased lipid oxidation   (MGI Ref ID J:130021)
  • decreased triglyceride level
    • during hyperinsulinemic-euglycemic clamps, intramuscular triglyceride levels are reduced by almost 90%   (MGI Ref ID J:130021)
    • decreased circulating triglyceride level
      • following an overnight fast and phloridzin treatment to lower plasma glucose levels, basal plasma triglyceride levels are reduced by 40%   (MGI Ref ID J:130021)
      • however, the insulin clamp has no effect on plasma triglyceride levels in mutants compared to wild-type mice in which there is a 50% reduction   (MGI Ref ID J:130021)
    • decreased liver triglyceride level
      • intrahepatic triglyceride levels are reduced during hyperinsulinemic-euglycemic clamps   (MGI Ref ID J:130021)
  • increased carbon dioxide production
    • both rate of oxygen consumption and carbon dioxide production are increased by about 40%   (MGI Ref ID J:130021)
  • increased energy expenditure
    • mutants show increased energy expenditure during a 24 hour cycle   (MGI Ref ID J:130021)
  • increased oxygen consumption
    • both rate of oxygen consumption and carbon dioxide production are increased by about 40%   (MGI Ref ID J:130021)
  • cardiovascular system phenotype
  • abnormal cardiac muscle contractility
    • ventricular fractional shortening and ejection fraction are altered in mutants   (MGI Ref ID J:130021)
    • chronic treatment with phloridzin to chronically lower circulating glucose levels normalizes cardiac function   (MGI Ref ID J:130021)
  • abnormal heart morphology
    • cardiac remodeling   (MGI Ref ID J:130021)
    • abnormal heart left ventricle morphology
      • left ventricular posterior wall thickness is increased   (MGI Ref ID J:130021)
      • heart left ventricle hypertrophy
        • ventricular hypertrophy   (MGI Ref ID J:130021)
    • thick interventricular septum   (MGI Ref ID J:130021)
  • liver/biliary system phenotype
  • decreased liver triglyceride level
    • intrahepatic triglyceride levels are reduced during hyperinsulinemic-euglycemic clamps   (MGI Ref ID J:130021)
  • muscle phenotype
  • abnormal cardiac muscle contractility
    • ventricular fractional shortening and ejection fraction are altered in mutants   (MGI Ref ID J:130021)
    • chronic treatment with phloridzin to chronically lower circulating glucose levels normalizes cardiac function   (MGI Ref ID J:130021)
  • abnormal muscle cell glucose uptake
    • during hyperinsulinemic-euglycemic clamps, skeletal muscle glucose uptake is reduced by about 30%   (MGI Ref ID J:130021)
    • chronic treatment with phloridzin to chronically lower circulating glucose levels improves muscle glucose metabolism   (MGI Ref ID J:130021)
View Research Applications

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

Developmental Biology Research

Research Tools
Developmental Biology Research

Ins2Akita 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 provided by MGI

 
Allele Symbol Ins2Akita
Allele Name Akita
Allele Type Spontaneous
Common Name(s) Akita; AkitaIns2; Ins2C96Y; Ins2Mody; Mody; Mody4;
Strain of OriginC57BL/6NSlc
Gene Symbol and Name Ins2, insulin II
Chromosome 7
Gene Common Name(s) AA986540; IDDM1; IDDM2; ILPR; IRDN; Ins-2; InsII; MODY10; Mody; Mody4; expressed sequence AA986540; maturity onset diabetes of the young; maturity onset diabetes of the young 4;
General Note Phenotypic Similarity to Human Syndrome: Type 1 Diabetic Macrovascular Disease (J:174983)
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

Ins2Akita, End Point Analysis
Ins2Akita, Restriction Enzyme Digest


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Ins2Akita related

Aghdam SY; Gurel Z; Ghaffarieh A; Sorenson CM; Sheibani N. 2013. High glucose and diabetes modulate cellular proteasome function: Implications in the pathogenesis of diabetes complications. Biochem Biophys Res Commun 432(2):339-44. [PubMed: 23391566]  [MGI Ref ID J:198848]

Akimov NP; Renteria RC. 2012. Spatial frequency threshold and contrast sensitivity of an optomotor behavior are impaired in the Ins2Akita mouse model of diabetes. Behav Brain Res 226(2):601-5. [PubMed: 21963766]  [MGI Ref ID J:180197]

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]

Awad AS; Kinsey GR; Khutsishvili K; Gao T; Bolton WK; Okusa MD. 2011. Monocyte/macrophage chemokine receptor CCR2 mediates diabetic renal injury. Am J Physiol Renal Physiol 301(6):F1358-66. [PubMed: 21880831]  [MGI Ref ID J:180042]

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]

Basu R; Lee J; Wang Z; Patel VB; Fan D; Das SK; Liu GC; John R; Scholey JW; Oudit GY; Kassiri Z. 2012. Loss of TIMP3 selectively exacerbates diabetic nephropathy. Am J Physiol Renal Physiol 303(9):F1341-52. [PubMed: 22896043]  [MGI Ref ID J:189948]

Basu R; Oudit GY; Wang X; Zhang L; Ussher JR; Lopaschuk GD; Kassiri Z. 2009. Type 1 diabetic cardiomyopathy in the Akita (Ins2WT/C96Y) mouse model is characterized by lipotoxicity and diastolic dysfunction with preserved systolic function. Am J Physiol Heart Circ Physiol 297(6):H2096-108. [PubMed: 19801494]  [MGI Ref ID J:158228]

Bostrom KI; Jumabay M; Matveyenko A; Nicholas SB; Yao Y. 2011. Activation of vascular bone morphogenetic protein signaling in diabetes mellitus. Circ Res 108(4):446-57. [PubMed: 21193740]  [MGI Ref ID J:183498]

Bugger H; Boudina S; Hu XX; Tuinei J; Zaha VG; Theobald HA; Yun UJ; McQueen AP; Wayment B; Litwin SE; Abel ED. 2008. Type 1 diabetic akita mouse hearts are insulin sensitive but manifest structurally abnormal mitochondria that remain coupled despite increased uncoupling protein 3. Diabetes 57(11):2924-32. [PubMed: 18678617]  [MGI Ref ID J:142159]

Bugger H; Chen D; Riehle C; Soto J; Theobald HA; Hu XX; Ganesan B; Weimer BC; Abel ED. 2009. Tissue-specific remodeling of the mitochondrial proteome in type 1 diabetic akita mice. Diabetes 58(9):1986-97. [PubMed: 19542201]  [MGI Ref ID J:154406]

Chacko BK; Reily C; Srivastava A; Johnson MS; Ye Y; Ulasova E; Agarwal A; Zinn KR; Murphy MP; Kalyanaraman B; Darley-Usmar V. 2010. Prevention of diabetic nephropathy in Ins2(+/)(AkitaJ) mice by the mitochondria-targeted therapy MitoQ. Biochem J 432(1):9-19. [PubMed: 20825366]  [MGI Ref ID J:166866]

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]

Chang JH; Paik SY; Mao L; Eisner W; Flannery PJ; Wang L; Tang Y; Mattocks N; Hadjadj S; Goujon JM; Ruiz P; Gurley SB; Spurney RF. 2012. Diabetic kidney disease in FVB/NJ Akita mice: temporal pattern of kidney injury and urinary nephrin excretion. PLoS One 7(4):e33942. [PubMed: 22496773]  [MGI Ref ID J:187110]

Chavali V; Tyagi SC; Mishra PK. 2012. MicroRNA-133a regulates DNA methylation in diabetic cardiomyocytes. Biochem Biophys Res Commun 425(3):668-72. [PubMed: 22842467]  [MGI Ref ID J:188036]

Cheng L; Han X; Shi Y. 2009. A regulatory role of LPCAT1 in the synthesis of inflammatory lipids, PAF and LPC, in the retina of diabetic mice. Am J Physiol Endocrinol Metab 297(6):E1276-82. [PubMed: 19773578]  [MGI Ref ID J:159566]

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]

Dennis MD; Schrufer TL; Bronson SK; Kimball SR; Jefferson LS. 2011. Hyperglycemia-Induced O-GlcNAcylation and Truncation of 4E-BP1 Protein in Liver of a Mouse Model of Type 1 Diabetes. J Biol Chem 286(39):34286-97. [PubMed: 21840999]  [MGI Ref ID J:176719]

Drapeau N; Lizotte F; Denhez B; Guay A; Kennedy CR; Geraldes P. 2013. Expression of SHP-1 induced by hyperglycemia prevents insulin actions in podocytes. Am J Physiol Endocrinol Metab 304(11):E1188-98. [PubMed: 23531619]  [MGI Ref ID J:198982]

Dugan LL; You YH; Ali SS; Diamond-Stanic M; Miyamoto S; DeCleves AE; Andreyev A; Quach T; Ly S; Shekhtman G; Nguyen W; Chepetan A; Le TP; Wang L; Xu M; Paik KP; Fogo A; Viollet B; Murphy A; Brosius F; Naviaux RK; Sharma K. 2013. AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function. J Clin Invest 123(11):4888-99. [PubMed: 24135141]  [MGI Ref ID J:204683]

Fang RC; Kryger ZB; Buck Ii DW; De La Garza M; Galiano RD; Mustoe TA. 2010. Limitations of the db/db mouse in translational wound healing research: Is the NONcNZO10 polygenic mouse model superior? Wound Repair Regen :. [PubMed: 20955341]  [MGI Ref ID J:165705]

Faulhaber-Walter R; Chen L; Oppermann M; Kim SM; Huang Y; Hiramatsu N; Mizel D; Kajiyama H; Zerfas P; Briggs JP; Kopp JB; Schnermann J. 2008. Lack of A1 adenosine receptors augments diabetic hyperfiltration and glomerular injury. J Am Soc Nephrol 19(4):722-30. [PubMed: 18256360]  [MGI Ref ID J:149926]

Fox R; Kim HS; Reddick RL; Kujoth GC; Prolla TA; Tsutsumi S; Wada Y; Smithies O; Maeda N. 2011. Mitochondrial DNA polymerase editing mutation, PolgD257A, reduces the diabetic phenotype of Akita male mice by suppressing appetite. Proc Natl Acad Sci U S A 108(21):8779-84. [PubMed: 21555558]  [MGI Ref ID J:171899]

Fox TE; Bewley MC; Unrath KA; Pedersen MM; Anderson RE; Jung DY; Jefferson LS; Kim JK; Bronson SK; Flanagan JM; Kester M. 2011. Circulating sphingolipid biomarkers in models of type 1 diabetes. J Lipid Res 52(3):509-17. [PubMed: 21068007]  [MGI Ref ID J:170277]

Gambhir D; Ananth S; Veeranan-Karmegam R; Elangovan S; Hester S; Jennings E; Offermanns S; Nussbaum JJ; Smith SB; Thangaraju M; Ganapathy V; Martin PM. 2012. GPR109A as an anti-inflammatory receptor in retinal pigment epithelial cells and its relevance to diabetic retinopathy. Invest Ophthalmol Vis Sci 53(4):2208-17. [PubMed: 22427566]  [MGI Ref ID J:196849]

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]

Grasemann C; Devlin MJ; Rzeczkowska PA; Herrmann R; Horsthemke B; Hauffa BP; Grynpas M; Alm C; Bouxsein ML; Palmert MR. 2012. Parental diabetes: the Akita mouse as a model of the effects of maternal and paternal hyperglycemia in wildtype offspring. PLoS One 7(11):e50210. [PubMed: 23209676]  [MGI Ref ID J:195000]

Grutzmacher C; Park S; Zhao Y; Morrison ME; Sheibani N; Sorenson CM. 2013. Aberrant production of extracellular matrix proteins and dysfunction in kidney endothelial cells with a short duration of diabetes. Am J Physiol Renal Physiol 304(1):F19-30. [PubMed: 23077100]  [MGI Ref ID J:191244]

Gupta S; McGrath B; Cavener DR. 2010. PERK (EIF2AK3) regulates proinsulin trafficking and quality control in the secretory pathway. Diabetes 59(8):1937-47. [PubMed: 20530744]  [MGI Ref ID J:169638]

Gurel Z; Sieg KM; Shallow KD; Sorenson CM; Sheibani N. 2013. Retinal O-linked N-acetylglucosamine protein modifications: implications for postnatal retinal vascularization and the pathogenesis of diabetic retinopathy. Mol Vis 19:1047-59. [PubMed: 23734074]  [MGI Ref ID J:203213]

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]

Gurley SB; Mach CL; Stegbauer J; Yang J; Snow KP; Hu A; Meyer TW; Coffman TM. 2010. Influence of genetic background on albuminuria and kidney injury in Ins2(+/C96Y) (Akita) mice. Am J Physiol Renal Physiol 298(3):F788-95. [PubMed: 20042456]  [MGI Ref ID J:157873]

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]

Ha Y; Dun Y; Thangaraju M; Duplantier J; Dong Z; Liu K; Ganapathy V; Smith SB. 2011. Sigma receptor 1 modulates endoplasmic reticulum stress in retinal neurons. Invest Ophthalmol Vis Sci 52(1):527-40. [PubMed: 20811050]  [MGI Ref ID J:171562]

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]

Hodish I; Absood A; Liu L; Liu M; Haataja L; Larkin D; Al-Khafaji A; Zaki A; Arvan P. 2011. In vivo misfolding of proinsulin below the threshold of frank diabetes. Diabetes 60(8):2092-101. [PubMed: 21677281]  [MGI Ref ID J:186814]

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]

Howard AC; McNeil AK; Xiong F; Xiong WC; McNeil PL. 2011. A novel cellular defect in diabetes: membrane repair failure. Diabetes 60(11):3034-43. [PubMed: 21940783]  [MGI Ref ID J:189473]

Howell SJ; Mekhail MN; Azem R; Ward NL; Kern TS. 2013. Degeneration of retinal ganglion cells in diabetic dogs and mice: relationship to glycemic control and retinal capillary degeneration. Mol Vis 19:1413-21. [PubMed: 23825921]  [MGI Ref ID J:200768]

Hu Y; Chen Y; Ding L; He X; Takahashi Y; Gao Y; Shen W; Cheng R; Chen Q; Qi X; Boulton ME; Ma JX. 2013. Pathogenic role of diabetes-induced PPAR-alpha down-regulation in microvascular dysfunction. Proc Natl Acad Sci U S A 110(38):15401-6. [PubMed: 24003152]  [MGI Ref ID J:201158]

Huang H; Gandhi JK; Zhong X; Wei Y; Gong J; Duh EJ; Vinores SA. 2011. TNFalpha is required for late BRB breakdown in diabetic retinopathy, and its inhibition prevents leukostasis and protects vessels and neurons from apoptosis. Invest Ophthalmol Vis Sci 52(3):1336-44. [PubMed: 21212173]  [MGI Ref ID J:171543]

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]

Jaholkowski P; Mierzejewski P; Zatorski P; Scinska A; Sienkiewicz-Jarosz H; Kaczmarek L; Samochowiec J; Filipkowski RK; Bienkowski P. 2011. Increased ethanol intake and preference in cyclin D2 knockout mice. Genes Brain Behav 10(5):551-6. [PubMed: 21429093]  [MGI Ref ID J:185702]

Johnson LA; Kim HS; Knudson MJ; Nipp CT; Yi X; Maeda N. 2013. Diabetic atherosclerosis in APOE*4 mice: synergy between lipoprotein metabolism and vascular inflammation. J Lipid Res 54(2):386-96. [PubMed: 23204275]  [MGI Ref ID J:193106]

Jun JY; Ma Z; Segar L. 2011. Spontaneously diabetic Ins2(+/Akita):apoE-deficient mice exhibit exaggerated hypercholesterolemia and atherosclerosis. Am J Physiol Endocrinol Metab 301(1):E145-54. [PubMed: 21447785]  [MGI Ref ID J:182074]

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; Sullivan KA; Backus C; Hayes JM; Oh SS; Hua K; Gasim AM; Tomita H; Grant R; Nossov SB; Kim HS; Jennette JC; Feldman EL; Smithies O. 2010. Lack of both bradykinin B1 and B2 receptors enhances nephropathy, neuropathy, and bone mineral loss in Akita diabetic mice. Proc Natl Acad Sci U S A 107(22):10190-5. [PubMed: 20479236]  [MGI Ref ID J:161075]

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]

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]

Kern TS; Tang J; Berkowitz BA. 2010. Validation of structural and functional lesions of diabetic retinopathy in mice. Mol Vis 16:2121-31. [PubMed: 21139688]  [MGI Ref ID J:168105]

Kim ST; Moley KH. 2008. Paternal effect on embryo quality in diabetic mice is related to poor sperm quality and associated with decreased glucose transporter expression. Reproduction 136(3):313-22. [PubMed: 18558660]  [MGI Ref ID J:145654]

Kobayashi H; Yamazaki S; Takashima S; Liu W; Okuda H; Yan J; Fujii Y; Hitomi T; Harada KH; Habu T; Koizumi A. 2013. Ablation of Rnf213 retards progression of diabetes in the Akita mouse. Biochem Biophys Res Commun 432(3):519-25. [PubMed: 23410753]  [MGI Ref ID J:200802]

Krause MP; Al-Sajee D; D'Souza DM; Rebalka IA; Moradi J; Riddell MC; Hawke TJ. 2013. Impaired macrophage and satellite cell infiltration occurs in a muscle-specific fashion following injury in diabetic skeletal muscle. PLoS One 8(8):e70971. [PubMed: 23951058]  [MGI Ref ID J:205890]

Krause MP; Moradi J; Nissar AA; Riddell MC; Hawke TJ. 2011. Inhibition of plasminogen activator inhibitor-1 restores skeletal muscle regeneration in untreated type 1 diabetic mice. Diabetes 60(7):1964-72. [PubMed: 21593201]  [MGI Ref ID J:186757]

LaRocca TJ; Fabris F; Chen J; Benhayon D; Zhang S; McCollum L; Schecter AD; Cheung JY; Sobie EA; Hajjar RJ; Lebeche D. 2012. Na+/Ca2+ exchanger-1 protects against systolic failure in the Akitains2 model of diabetic cardiomyopathy via a CXCR4/NF-kappaB pathway. Am J Physiol Heart Circ Physiol 303(3):H353-67. [PubMed: 22610174]  [MGI Ref ID J:189027]

Lee AH; Heidtman K; Hotamisligil GS; Glimcher LH. 2011. Dual and opposing roles of the unfolded protein response regulated by IRE1{alpha} and XBP1 in proinsulin processing and insulin secretion. Proc Natl Acad Sci U S A 108(21):8885-90. [PubMed: 21555585]  [MGI Ref ID J:171889]

Lerner AG; Upton JP; Praveen PV; Ghosh R; Nakagawa Y; Igbaria A; Shen S; Nguyen V; Backes BJ; Heiman M; Heintz N; Greengard P; Hui S; Tang Q; Trusina A; Oakes SA; Papa FR. 2012. IRE1alpha Induces Thioredoxin-Interacting Protein to Activate the NLRP3 Inflammasome and Promote Programmed Cell Death under Irremediable ER Stress. Cell Metab 16(2):250-64. [PubMed: 22883233]  [MGI Ref ID J:187377]

Li J; Wang JJ; Yu Q; Wang M; Zhang SX. 2009. Endoplasmic reticulum stress is implicated in retinal inflammation and diabetic retinopathy. FEBS Lett 583(9):1521-7. [PubMed: 19364508]  [MGI Ref ID J:148021]

Liu GC; Fang F; Zhou J; Koulajian K; Yang S; Lam L; Reich HN; John R; Herzenberg AM; Giacca A; Oudit GY; Scholey JW. 2012. Deletion of p47 ( phox ) attenuates the progression of diabetic nephropathy and reduces the severity of diabetes in the Akita mouse. Diabetologia 55(9):2522-32. [PubMed: 22653270]  [MGI Ref ID J:186435]

Liu J; Gao BB; Clermont AC; Blair P; Chilcote TJ; Sinha S; Flaumenhaft R; Feener EP. 2011. Hyperglycemia-induced cerebral hematoma expansion is mediated by plasma kallikrein. Nat Med 17(2):206-10. [PubMed: 21258336]  [MGI Ref ID J:168556]

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]

Lo CS; Liu F; Shi Y; Maachi H; Chenier I; Godin N; Filep JG; Ingelfinger JR; Zhang SL; Chan JS. 2012. Dual RAS blockade normalizes angiotensin-converting enzyme-2 expression and prevents hypertension and tubular apoptosis in Akita angiotensinogen-transgenic mice. Am J Physiol Renal Physiol 302(7):F840-52. [PubMed: 22205225]  [MGI Ref ID J:182441]

Lorenzen J; Shah R; Biser A; Staicu SA; Niranjan T; Garcia AM; Gruenwald A; Thomas DB; Shatat IF; Supe K; Woroniecki RP; Susztak K. 2008. The role of osteopontin in the development of albuminuria. J Am Soc Nephrol 19(5):884-90. [PubMed: 18443355]  [MGI Ref ID J:150239]

Losiewicz MK; Fort PE. 2011. Diabetes impairs the neuroprotective properties of retinal alpha-crystallins. Invest Ophthalmol Vis Sci 52(9):5034-42. [PubMed: 21467180]  [MGI Ref ID J:181425]

Lu A; Miao M; Schoeb TR; Agarwal A; Murphy-Ullrich JE. 2011. Blockade of TSP1-Dependent TGF-beta Activity Reduces Renal Injury and Proteinuria in a Murine Model of Diabetic Nephropathy. Am J Pathol 178(6):2573-86. [PubMed: 21641382]  [MGI Ref ID J:173296]

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]

Martens GW; Arikan MC; Lee J; Ren F; Greiner D; Kornfeld H. 2007. Tuberculosis susceptibility of diabetic mice. Am J Respir Cell Mol Biol 37(5):518-24. [PubMed: 17585110]  [MGI Ref ID J:141650]

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]

Matsuda T; Kido Y; Asahara S; Kaisho T; Tanaka T; Hashimoto N; Shigeyama Y; Takeda A; Inoue T; Shibutani Y; Koyanagi M; Hosooka T; Matsumoto M; Inoue H; Uchida T; Koike M; Uchiyama Y; Akira S; Kasuga M. 2010. Ablation of C/EBPbeta alleviates ER stress and pancreatic beta cell failure through the GRP78 chaperone in mice. J Clin Invest 120(1):115-26. [PubMed: 19955657]  [MGI Ref ID J:156725]

Mishra PK; Givvimani S; Metreveli N; Tyagi SC. 2010. Attenuation of beta2-adrenergic receptors and homocysteine metabolic enzymes cause diabetic cardiomyopathy. Biochem Biophys Res Commun 401(2):175-81. [PubMed: 20836991]  [MGI Ref ID J:165848]

Mitchell T; Johnson MS; Ouyang X; Chacko BK; Mitra K; Lei X; Gai Y; Moore DR; Barnes S; Zhang J; Koizumi A; Ramanadham S; Darley-Usmar VM. 2013. Dysfunctional mitochondrial bioenergetics and oxidative stress in Akita(+/Ins2)-derived beta-cells. Am J Physiol Endocrinol Metab 305(5):E585-99. [PubMed: 23820623]  [MGI Ref ID J:203191]

Mochida T; Tanaka T; Shiraki Y; Tajiri H; Matsumoto S; Shimbo K; Ando T; Nakamura K; Okamoto M; Endo F. 2011. Time-dependent changes in the plasma amino acid concentration in diabetes mellitus. Mol Genet Metab 103(4):406-9. [PubMed: 21636301]  [MGI Ref ID J:174793]

Morris SM Jr; Gao T; Cooper TK; Kepka-Lenhart D; Awad AS. 2011. Arginase-2 mediates diabetic renal injury. Diabetes 60(11):3015-22. [PubMed: 21926276]  [MGI Ref ID J:189484]

Nagareddy PR; Murphy AJ; Stirzaker RA; Hu Y; Yu S; Miller RG; Ramkhelawon B; Distel E; Westerterp M; Huang LS; Schmidt AM; Orchard TJ; Fisher EA; Tall AR; Goldberg IJ. 2013. Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis. Cell Metab 17(5):695-708. [PubMed: 23663738]  [MGI Ref ID J:199272]

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]

Nicholas SB; Liu J; Kim J; Ren Y; Collins AR; Nguyen L; Hsueh WA. 2010. Critical role for osteopontin in diabetic nephropathy. Kidney Int 77(7):588-600. [PubMed: 20130530]  [MGI Ref ID J:184276]

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]

Okamoto K; Iwasaki N; Doi K; Noiri E; Iwamoto Y; Uchigata Y; Fujita T; Tokunaga K. 2012. Inhibition of glucose-stimulated insulin secretion by KCNJ15, a newly identified susceptibility gene for type 2 diabetes. Diabetes 61(7):1734-41. [PubMed: 22566534]  [MGI Ref ID J:203172]

Oudit GY; Liu GC; Zhong J; Basu R; Chow FL; Zhou J; Loibner H; Janzek E; Schuster M; Penninger JM; Herzenberg AM; Kassiri Z; Scholey JW. 2010. Human recombinant ACE2 reduces the progression of diabetic nephropathy. Diabetes 59(2):529-38. [PubMed: 19934006]  [MGI Ref ID J:164158]

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]

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]

Park HJ; Zhang Y; Du C; Welzig CM; Madias C; Aronovitz MJ; Georgescu SP; Naggar I; Wang B; Kim YB; Blaustein RO; Karas RH; Liao R; Mathews CE; Galper JB. 2009. Role of SREBP-1 in the development of parasympathetic dysfunction in the hearts of type 1 diabetic Akita mice. Circ Res 105(3):287-94. [PubMed: 19423844]  [MGI Ref ID J:164764]

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]

Pendse AA; Johnson LA; Tsai YS; Maeda N. 2010. Pparg-P465L mutation worsens hyperglycemia in Ins2-Akita female mice via adipose-specific insulin resistance and storage dysfunction. Diabetes 59(11):2890-7. [PubMed: 20724579]  [MGI Ref ID J:169338]

Pfister F; Feng Y; vom Hagen F; Hoffmann S; Molema G; Hillebrands JL; Shani M; Deutsch U; Hammes HP. 2008. Pericyte migration: a novel mechanism of pericyte loss in experimental diabetic retinopathy. Diabetes 57(9):2495-502. [PubMed: 18559662]  [MGI Ref ID J:141775]

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]

Queisser MA; Yao D; Geisler S; Hammes HP; Lochnit G; Schleicher ED; Brownlee M; Preissner KT. 2010. Hyperglycemia impairs proteasome function by methylglyoxal. Diabetes 59(3):670-8. [PubMed: 20009088]  [MGI Ref ID J:164153]

Rakoczy EP; Ali Rahman IS; Binz N; Li CR; Vagaja NN; de Pinho M; Lai CM. 2010. Characterization of a mouse model of hyperglycemia and retinal neovascularization. Am J Pathol 177(5):2659-70. [PubMed: 20829433]  [MGI Ref ID J:166270]

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]

Schmidt RE; Feng D; Wang Q; Green KG; Snipes LL; Yamin M; Brines M. 2011. Effect of insulin and an erythropoietin-derived peptide (ARA290) on established neuritic dystrophy and neuronopathy in Akita (Ins2 Akita) diabetic mouse sympathetic ganglia. Exp Neurol 232(2):126-35. [PubMed: 21872588]  [MGI Ref ID J:178385]

Schmidt RE; Green KG; Snipes LL; Feng D. 2009. Neuritic dystrophy and neuronopathy in Akita (Ins2(Akita)) diabetic mouse sympathetic ganglia. Exp Neurol 216(1):207-18. [PubMed: 19111542]  [MGI Ref ID J:146204]

Schoeller EL; Albanna G; Frolova AI; Moley KH. 2012. Insulin rescues impaired spermatogenesis via the hypothalamic-pituitary-gonadal axis in Akita diabetic mice and restores male fertility. Diabetes 61(7):1869-78. [PubMed: 22522616]  [MGI Ref ID J:203174]

Schrufer TL; Antonetti DA; Sonenberg N; Kimball SR; Gardner TW; Jefferson LS. 2010. Ablation of 4E-BP1/2 prevents hyperglycemia-mediated induction of VEGF expression in the rodent retina and in Muller cells in culture. Diabetes 59(9):2107-16. [PubMed: 20547975]  [MGI Ref ID J:169349]

Shi Y; Lo CS; Chenier I; Maachi H; Filep JG; Ingelfinger JR; Zhang SL; Chan JS. 2013. Overexpression of catalase prevents hypertension and tubulointerstitial fibrosis and normalization of renal angiotensin-converting enzyme-2 expression in Akita mice. Am J Physiol Renal Physiol 304(11):F1335-46. [PubMed: 23552863]  [MGI Ref ID J:197243]

Sklavos MM; Bertera S; Tse HM; Bottino R; He J; Beilke JN; Coulombe MG; Gill RG; Crapo JD; Trucco M; Piganelli JD. 2010. Redox modulation protects islets from transplant-related injury. Diabetes 59(7):1731-8. [PubMed: 20413509]  [MGI Ref ID J:169646]

Smith SB; Duplantier J; Dun Y; Mysona B; Roon P; Martin PM; Ganapathy V. 2008. In vivo protection against retinal neurodegeneration by sigma receptor 1 ligand (+)-pentazocine. Invest Ophthalmol Vis Sci 49(9):4154-61. [PubMed: 18469181]  [MGI Ref ID J:141696]

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]

Toque HA; Nunes KP; Yao L; Xu Z; Kondrikov D; Su Y; Webb RC; Caldwell RB; Caldwell RW. 2013. Akita spontaneously type 1 diabetic mice exhibit elevated vascular arginase and impaired vascular endothelial and nitrergic function. PLoS One 8(8):e72277. [PubMed: 23977269]  [MGI Ref ID J:206426]

Vagaja NN; Chinnery HR; Binz N; Kezic JM; Rakoczy EP; McMenamin PG. 2012. Changes in murine hyalocytes are valuable early indicators of ocular disease. Invest Ophthalmol Vis Sci 53(3):1445-51. [PubMed: 22297487]  [MGI Ref ID J:196754]

Vallon V; Gerasimova M; Rose MA; Masuda T; Satriano J; Mayoux E; Koepsell H; Thomson SC; Rieg T. 2014. SGLT2 inhibitor empagliflozin reduces renal growth and albuminuria in proportion to hyperglycemia and prevents glomerular hyperfiltration in diabetic Akita mice. Am J Physiol Renal Physiol 306(2):F194-204. [PubMed: 24226524]  [MGI Ref ID J:205116]

Vallon V; Rose M; Gerasimova M; Satriano J; Platt KA; Koepsell H; Cunard R; Sharma K; Thomson SC; Rieg T. 2013. Knockout of Na-glucose transporter SGLT2 attenuates hyperglycemia and glomerular hyperfiltration but not kidney growth or injury in diabetes mellitus. Am J Physiol Renal Physiol 304(2):F156-67. [PubMed: 23152292]  [MGI Ref ID J:192346]

Vashistha H; Singhal PC; Malhotra A; Husain M; Mathieson P; Saleem MA; Kuriakose C; Seshan S; Wilk A; Delvalle L; Peruzzi F; Giorgio M; Pelicci PG; Smithies O; Kim HS; Kakoki M; Reiss K; Meggs LG. 2012. Null mutations at the p66 and bradykinin 2 receptor loci induce divergent phenotypes in the diabetic kidney. Am J Physiol Renal Physiol 303(12):F1629-40. [PubMed: 23019230]  [MGI Ref ID J:190320]

Wang CH; Li F; Hiller S; Kim HS; Maeda N; Smithies O; Takahashi N. 2011. A modest decrease in endothelial NOS in mice comparable to that associated with human NOS3 variants exacerbates diabetic nephropathy. Proc Natl Acad Sci U S A 108(5):2070-5. [PubMed: 21245338]  [MGI Ref ID J:169115]

Wang J; Chen Y; Yuan Q; Tang W; Zhang X; Osei K. 2011. Control of Precursor Maturation and Disposal Is an Early Regulative Mechanism in the Normal Insulin Production of Pancreatic beta-Cells. PLoS One 6(4):e19446. [PubMed: 21559376]  [MGI Ref ID J:172346]

Wang J; Osei K. 2011. Proinsulin maturation disorder is a contributor to the defect of subsequent conversion to insulin in beta-cells. Biochem Biophys Res Commun 411(1):150-5. [PubMed: 21723250]  [MGI Ref ID J:174771]

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]

Wang Q; Frolova AI; Purcell S; Adastra K; Schoeller E; Chi MM; Schedl T; Moley KH. 2010. Mitochondrial dysfunction and apoptosis in cumulus cells of type I diabetic mice. PLoS One 5(12):e15901. [PubMed: 21209947]  [MGI Ref ID J:168309]

Wende AR; Soto J; Olsen CD; Pires KM; Schell JC; Larrieu-Lahargue F; Litwin SE; Kakoki M; Takahashi N; Smithies O; Abel ED. 2010. Loss of Bradykinin Signaling Does Not Accelerate the Development of Cardiac Dysfunction in Type 1 Diabetic Akita Mice. Endocrinology :. [PubMed: 20501666]  [MGI Ref ID J:161074]

Winnay JN; Dirice E; Liew CW; Kulkarni RN; Kahn CR. 2014. p85alpha deficiency protects beta-cells from endoplasmic reticulum stress-induced apoptosis. Proc Natl Acad Sci U S A 111(3):1192-7. [PubMed: 24395790]  [MGI Ref ID J:206472]

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]

Wright WS; Yadav AS; McElhatten RM; Harris NR. 2012. Retinal blood flow abnormalities following six months of hyperglycemia in the Ins2(Akita) mouse. Exp Eye Res 98:9-15. [PubMed: 22440813]  [MGI Ref ID J:196847]

Yamaguchi K; Takeda K; Kadowaki H; Ueda I; Namba Y; Ouchi Y; Nishitoh H; Ichijo H. 2013. Involvement of ASK1-p38 pathway in the pathogenesis of diabetes triggered by pancreatic ss cell exhaustion. Biochim Biophys Acta 1830(6):3656-63. [PubMed: 23416061]  [MGI Ref ID J:202436]

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]

Yeh CK; Harris SE; Mohan S; Horn D; Fajardo R; Chun YH; Jorgensen J; Macdougall M; Abboud-Werner S. 2012. Hyperglycemia and xerostomia are key determinants of tooth decay in type 1 diabetic mice. Lab Invest 92(6):868-82. [PubMed: 22449801]  [MGI Ref ID J:184712]

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]

Yu L; Su Y; Paueksakon P; Cheng H; Chen X; Wang H; Harris RC; Zent R; Pozzi A. 2012. Integrin alpha1/Akita double-knockout mice on a Balb/c background develop advanced features of human diabetic nephropathy. Kidney Int 81(11):1086-97. [PubMed: 22297672]  [MGI Ref ID J:198186]

Yuan Q; Tang W; Zhang X; Hinson JA; Liu C; Osei K; Wang J. 2012. Proinsulin atypical maturation and disposal induces extensive defects in mouse Ins2+/Akita beta-cells. PLoS One 7(4):e35098. [PubMed: 22509386]  [MGI Ref ID J:187092]

Zhou C; Pridgen B; King N; Xu J; Breslow JL. 2011. Hyperglycemic Ins2AkitaLdlr-/- mice show severely elevated lipid levels and increased atherosclerosis: a model of type 1 diabetic macrovascular disease. J Lipid Res 52(8):1483-93. [PubMed: 21606463]  [MGI Ref ID J:174983]

Zito E; Chin KT; Blais J; Harding HP; Ron D. 2010. ERO1-beta, a pancreas-specific disulfide oxidase, promotes insulin biogenesis and glucose homeostasis. J Cell Biol 188(6):821-32. [PubMed: 20308425]  [MGI Ref ID J:158805]

Zou MH; Li H; He C; Lin M; Lyons TJ; Xie Z. 2011. Tyrosine nitration of prostacyclin synthase is associated with enhanced retinal cell apoptosis in diabetes. Am J Pathol 179(6):2835-44. [PubMed: 22015457]  [MGI Ref ID J:180271]

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]

de Preux Charles AS; Verdier V; Zenker J; Peter B; Medard JJ; Kuntzer T; Beckmann JS; Bergmann S; Chrast R. 2010. Global transcriptional programs in peripheral nerve endoneurium and DRG are resistant to the onset of type 1 diabetic neuropathy in Ins2 mice. PLoS One 5(5):e10832. [PubMed: 20520806]  [MGI Ref ID J:160899]

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 & HusbandryDonating investigator reports wildtype offspring of FVB/NJ, heterozygous, mutant females undergo fetal development in a hyperglycemic environment and exhibit hyperglycemia at weaning, are insulin resistant and may have islet abnormalities. Using the heterozygous mutant female for breeding can program diabetes/insulin resistance and confound the diabetic phenotype in the heterozygous mutant.
The breeding colony is currently maintained through mating FVB/NJ inbred or wild-type female with a heterozygous male. After onset of diabetes, when cages become very wet (due to diabetes-associated polyuria), the health of the heterozygous mutant is best maintained by housing them in cages containing a mixture of regular litter and Alpha-Dri, changed minimally twice a week.

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* $2085.00
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 11 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* $2710.50
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 11 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.

General Supply Notes

Control Information

  Control
   Wild-type from the colony
   001800 FVB/NJ
 
  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.


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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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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.


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