TGF-β1 Overexpression in Murine Pancreas Induces Chronic Pancreatitis and Together with TNF-α, Triggers Insulin-Dependent Diabetes

We have generated transgenic mice overexpressing TGF-β1 in pancreatic β cells. This resulted in massive fibrosis of the pancreas; in adult mice, most of the acini were replaced by fibrotic and adipose tissues. A conspicuous disorganisation of the islets of Langerhans was also observed, however, the number of β cells was not decreased and the mice were normoglycemic. Backcrossing to transgenic mice overexpressing TNF-α in their islet β cells (which also remain normoglycemic, (1)) yielded double transgenics, most of which became diabetic by the age of 4 months; histological analysis revealed a dramatic decrease in insulin-containing β cells. (Part of this work has been reported in abstract form, Experientia 51, p. A9, February 1995).