QUANTITATIVE-ANALYSIS OF GLUTAMATE-DECARB OXYLASE (GAD-65) GENE-EXPRESSION IN NOD MOUSE PANCREAS

Glutamate decarboxylase (GAD), especially the GAD 65 isoform, is a maj or autoantigen in autoimmune diabetes. To determine the role of GAD 65 in the pathogenesis of the disease, we developed a quantitative I)CR method allowing to establish the absolute number of GAD 65 mRNA molecu les expressed in pancreas of male and female non-obese diabetic (NOD) mice at 5 weeks of age, in comparison of the 2 non autoimmune mouse st rains. It appeared that pancreatic expression of GAD was similar in th e 3 strains (around 30 000 molecules/mu g total RNA) in males. However , in the NOD mouse, sexual dimorphism was observed with low GAD 65 exp ression in the female known to show higher incidence of the disease th an the male. This finding could contribute to the absence of GAD 65 to lerance in the female and suggests an hormonal control of GAD 65 gene expression.