The expression of influenza virus hemagglutinin in the pancreatic β cells of transgenic mice results in autoimmune diabetes

Insulin-dependent diabetes mellitus results from the autoimmune destruction of the insulin-producing β cells of the pancreatic islets. The target antigen(s) involved in this immunopathological process has not been identified. Our strategy was to determine whether expression of a novel surface antigen by murine pancreatic β cells would result in insulin-dependent diabetes mellitus. We have generated lines of transgenic mice (RIP-HA) that express the hemagglutinin of the A/Japan/305/57 strain of influenza virus on their insulin-producing β cells. Hyperglycemia developed in mice derived from all three founders at a frequency varying from 13% to 27%, and was associated with lymphocytic infiltration of the islets and a humoral response against β cell antigens, including hemagglutinin. These results suggest that the RIP-HA mice should provide a useful system in which to study the cellular interactions involved in the induction of self-tolerance and autoimmunity.