Mice heterozygous for the targeted mutation are viable and fertile, glucose tolerant, have normal blood sugar levels, serum lipid profiles and white adipose tissue mass.
No protein from the targeted gene was detected by Western Blot analysis of mice homozygous for the allele. Homozygous mice consume more food, have decreased adipose tissue mass and are hyperlipidemic compared to wildtype controls post-weaning. At 4 weeks of age glucose levels are normal but insulin levels are 40% of wildtype controls. At 7 weeks of age clinical diabetes is present in both male and female of homozygous mice. Histological evaluation of pancreas from 21 week old homozygote animals revealed a significant reduction in the number of islets and decreased cytoplasmic to nuclear ratio in the islet cells and there was no insulitis nor phagocytosis of necrotic beta cell fragments. While there is a progressive loss of beta cells in aging homozygous mice, there is no loss of alpha, delta or PP cells. Electron microscopy reveals degranulated beta cells and hypertrophic and hyperplastic mitochodria.
This strain is useful in islet transplantation research, stem cell research and as a tool for studying the role of oxidative stress in diabetes.
