| Description |
DBA/2J 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 and progressive in the males than in the females and
include hyperglycemia, hypoinsulinemia, polydipsia, and
polyuria, beginning at approximately 3-4 weeks of age.
Obesity and insulitis do not accompany diabetes. Litter
sizes range from 2-8 pups. Heterozygous Akita males develop
albuminuria at two months of age. The albuminuria is
progressive such that by 6 months of age albumin/creatine
levels are approximately 600ug/mg. Additionally, it has been
reported that DBA/2J heterozygous mutant mice develop
diabetic nephropathy.
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| Phenotype Description |
D2.B6-Ins2/MatbJ
Available at Jackson Laboratories
http://jaxmice.jax.org/strain/007562.html
Although not studied in the DBA/2J heterozygotes, C57BL/6
heterozygous mutant 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, and 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 mutant 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, indicate that Ins2Akita
mice will serve as an excellent substitute for mice made
insulin dependent diabetic by treatment with alloxan or
streptozotocin. Heterozygous Akita mice are also ideally
suited to allogeneic or xenogeneic islet transplantation
protocols because treating the mice 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 nephropathy
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