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; how ever, 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.
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