TRANSGENIC MICE EXPRESSING IFN-GAMMA IN PANCREATIC BETA-CELLS ARE RESISTANT TO STREPTOZOTOCIN-INDUCED DIABETES

In 28 adult Ins-IFN-gamma transgenic mice, injection of high doses of streptozotocin (STZ; first injection, 300 mu g/g body weight; second i njection, 200 mu g/g body weight 4 h later) failed to induce severe hy perglycemia. To the contrary, 28 BALB/c mice developed diabetes mellit us after identical injections of STZ. Because the STZ-induced islet da mage was partially inhibited in Ins-IFN-gamma transgenic mice, their g lycemia levels became normal 4 days after STZ administration. Both tra nsgenic and BALB/c mice lost weight after receiving STZ, but the body weights of transgenic mice then returned to pretreatment levels in a n early parallel manner with the glycemia. Immunolabeling with insulin i dentified an unusual spreading pattern of insulin immunoreactivity. Ul trastructural observations confirmed that beta-cell necrosis and degra nulation were more severe in STZ-treated BALB/c than in Ins-IFN-gamma transgenic mice. Moreover, regeneration of pancreatic duct cells and i slet neogenesis were observed in the transgenic mice. Therefore, after STZ treatment, the Ins-IFN-gamma transgenic mice apparently were resi stant to the induction of severe diabetes, whereas their BALB/c age-ma tched counterparts succumbed to the disease.