| 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).
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| 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.
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