TGF-BETA-1 OVEREXPRESSION IN MURINE PANCREAS INDUCES CHRONIC-PANCREATITIS AND TOGETHER WITH TNF-ALPHA, TRIGGERS INSULIN-DEPENDENT DIABETES

We have generated transgenic mice overexpressing TGF-beta 1 in pancrea tic beta cells. This resulted in massive fibrosis of the pancreas; in adult mice, most of the acini were replaced by fibrotic and adipose ti ssues. A conspicuous disorganisation of the islets of Langerhans was a lso observed, however, the number of beta cells was not decreased and the mice were normoglycemic. Backcrossing to transgenic mice overexpre ssing TNF-alpha in their islet beta cells (which also remain normoglyc emic, (1)) yielded double transgenics, most of which became diabetic b y the age of 4 months; histological analysis revealed a dramatic decre ase in insulin-containing beta cells. (Part of this work has been repo rted in abstract form, Experientia 51, p. A9, February 1995). (C) 1995 Academic Press. Inc.