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Strain

FVB.B6-Ins2^Akita/MlnJ

Summary

Data Summary

Official Name	FVB.B6-Ins2^Akita/MlnJ
Common Name	FVB-Akita
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).
Development Status	Phenotyping ongoing
Creation Method	congenic
Background	FVB/NJ
Breeding Type	intercross
Breeding Generations	9
Phenotype Description	FVB.B6-Ins2/MlnJ Available from Jackson Laboratories http://jaxmice.jax.org/strain/006867.html 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.

Type	Count
Genomics - Modifications	1
Experiments	1

Genomic Information

Gene	Allele 1	Allele 2	Protocol
Ins2	point mutation - transition	point mutation - transition	Not Specified

OrderID	Order	Investigator	Experiment	Status	Measurements
22144	22144	Mei Hua Gao	Hyperinsulinemic Hyperglycemic clamp order #22144	Completed	3920

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