Quantitative analysis of glutamate decarboxylase (GAD 65) gene expression in NOD mouse pancreas

Glutamate decarboxylase (GAD), especially the GAD 65 isoform, is a major autoantigen in autoimmune diabetes. To determine the role of GAD 65 in the pathogenesis of the disease, we developed a quantitative PCR method allowing to establish the absolute number of GAD 65 mRNA molecules 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 strains. It appeared that pancreatic expression of GAD was similar in the 3 strains (around 30,000 molecules/micrograms total RNA) in males. However, in the NOD mouse, sexual dimorphism was observed with low GAD 65 expression in the female known to show higher incidence of the disease than the male. This finding could contribute to the absence of GAD 65 tolerance in the female and suggests an hormonal control of GAD 65 gene expression.