MOLECULAR MECHANISMS IN DIABETIC EMBRYOPATHY
University Of Nebraska Medical Center, Omaha NE
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Abstract
The investigator will use a transgenic model system to investigate the hypothesis that transcription factors required for normal pancreatic function may also play a role in the pathogenesis of diabetes and its complications. Transgenic mice with Isl-1 expression targeted to the neural tube exhibit severe neural tube defects. Transgenic mice with Isl-1 expression targeted to the posterior develop severe growth defects. These transgenic systems reproduce some of the characteristics defects associated with maternal diabetes. The investigator will determine the molecular basis for these defects and will identify target genes that are regulated by Isl-1, both positively and negatively. One such candidate, Punc, has already been identified and some of the studies will further characterize this gene. Finally, the regulation of Isl-1 will be investigated using deletion analysis of the Isl-1 promoter. It is hoped that understanding the effects of Isl-1 overexpression will lead to new reagents to study diabetic embryopathy.
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