FUNCTIONAL ROLE OF CYPHER IN THE HEART

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 扩张型心肌病（DCM）的特征是左心室扩张和收缩功能障碍，伴有心力衰竭的迹象，30-40%的病例是遗传性的。遗传异质性已被确定，在一些细胞骨架和肌节基因的突变引起DCM表型。Cypher是一种位于Z盘的细胞骨架蛋白，最近发现其突变与DCM相关。然而，Cypher在心脏中的作用和Cypher相关心肌病的潜在机制在很大程度上是未知的。为了了解Cypher在心脏中的功能作用，我们已经产生了几种遗传小鼠模型，包括全局Cypher敲除小鼠、心脏特异性Cypher敲除小鼠和同种型特异性Cypher敲除小鼠。如上所述，Cypher是一种细胞骨架蛋白，定位于z盘，我们希望进行TEM以研究这些敲除小鼠品系中是否存在结构改变。

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.