Ju Chen, PhD
Involvement of Cypher Specific Isoforms in Dilated Cardiomyopathy
University of California, San Diego, CA
2005 Amount Awarded – $50,000
Dilated cardiomyopathy (DCM), characterized by left ventricular dilation and systolic dysfunction with signs of heart failure, is genetically transmitted in 30-40% of cases. Genetic heterogeneity has been identified, with mutations in a number of cytoskeletal and sarcomeric genes causing a DCM phenotype. Specific mutations in the cytoskeletal protein cypher have recently been found in a large proportion of cases of dilated cardiomyopathy in children and adults. Two of the mutations, which have been characterized, are located within the same region (exon 6) of the cypher gene. The goals of this study are to generate three mouse lines, which will be models for these human mutations, and to perform preliminary characterization of them. One mouse line will have a deletion in exon 6 of cypher, and the others will have specific point mutations within exon 6 which are found in human patients. The objective will be to utilize these mouse models to model human disease and to gain an understanding of the biochemical pathways leading to cardiomyopathy. A basic understanding of these pathways will suggest therapeutic targets for cardiomyopathy and consequently heart failure.