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MGI Accession ID: MGI:3576691
J Number: J:97926
Other Accession IDs: Title: Calmodulin-induced early-onset diabetes in transgenic mice.
Authors: Epstein PN; Overbeek PA; Means AR
Journal: Cell
Volume: 58
Issue: 6
Date: 1989 Sep 22
Year: 1989
Pages: 1067-73
Review Status: Peer Reviewed

Abstract:

Calmodulin is implicated as the primary transducer of the calcium signal in pancreatic beta cells, where it is present at very high concentrations. We have produced three lines of transgenic mice carrying a calmodulin minigene regulated by the rat insulin II promoter. Immunohistochemistry and hybridization analyses indicated a 5-fold increase in the content of calmodulin and its mRNA in beta cells. Transgenic mice developed severe diabetes within hours of birth. The diabetes was progressive and characterized by elevated blood glucose and glucagon that coincided with reduced serum and pancreatic insulin. The disease appears to have both secretory and cell destruction components. beta Cell pathology was evident in the diabetic neonate but not in the fetus, suggesting that the early onset of diabetes exacerbated possible toxic effects of excess calmodulin. These animals provide a new diabetes model to evaluate how abnormal calcium homeostasis alters the carefully programmed secretory activity and development of the beta cell.

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