FUNCTIONAL ROLE OF CYPHER IN THE HEART

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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. Mutations in Cypher, a cytoskeletal protein localized at Z-disc, was recently identified to associate with DCM. However, the role of Cypher in the heart and the mechanism underlying Cypher related cardiomyopathy is largely unknown. To understand the functional role of Cypher in the heart, we have generated several genetic mouse models, including global Cypher knockout mouse, cardiac specific Cypher knockout mouse, and isoform specific Cypher knockout mouse. As mentioned above, Cypher is a cytoskeletal protein and localized at z disc, we would like to perform TEM to investigate whether there are structural alterations in these knockout mouse lines.