Transgenic mice are characterized by pancreatic beta cells that express a rat insulin promoter 7, Ins2, regulated transgene encoding a human B-cell autoantigen, GAD2. These mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. This NOD/Lt transgenic demonstrates a Y Chr. integration-site as only male progeny are transgenic. Expression of the transgene in the islets has been confirmed by RT-PCR and Western blot analysis. Southern analysis confirms 17 copies of the transgene are present, compared to the A-line that has 4-5 copies (Stock No. 5870). Elevated levels of GAD2 expression in transgenic B-cells do not influence non-fasting plasma levels of insulin and glucagon. At 50 weeks of age 55% of the transgenic males were diabetic, this is not significantly different from NOD/Lt male cohorts. Insulitis in 9 week old females is not significantly different between transgenics and controls.
This model provides a tool for studying at the role of autoantigens, specifically GAD2, in diabetes.
