CYPHER, Z LINE PROTEIN

CYPHER，Z 线蛋白

• 批准号: 7358025
• 负责人: Ju Chen
• 金额: $ 1.53万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7358025
• 关键词: CYPHER; LINE; PROTEIN

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. Cypher knockout mice display a severe form of congenital myopathy and die postnatally from functional failure in multiple striated muscles. Examination of striated muscle from the mutants using IVEM revealed that Cypher is not required for sarcomerogenesis or Z-line assembly, but rather is required for maintenance of the Z-line during muscle function. A manuscript on Cypher, a Z-line specific protein including high magnification electron microscopic tomography is now being prepared. The six isoforms of Cypher can be divided into skeletal or cardiac specific classes, based on the inclusion of skeletal or cardiac specific domains. Short and long isoforms share an N-terminal PDZ domain, but the three C-terminal LIM domains are unique to long isoforms. To investigate the function of splice variants in vivo, we have performed a rescue experiment of the Cypher null mutant by replacing the endogenous Cypher gene with cDNAs encoding either a short or long skeletal muscle isoform. In contrast to Cypher null mice, a percentage of mice that express only a short or a long skeletal muscle specific isoform can survive to at least one year of age. Although surviving mice exhibit muscle pathology, these results suggest that either isoform is sufficient to rescue the lethality associated with absence of Cypher.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。Cypher基因敲除小鼠表现出严重的先天性肌病，并在出生后死于多横纹肌功能衰竭。使用IVEM检查突变体的横纹肌显示Cypher不是肌肉增生或z线组装所必需的，而是在肌肉功能期间维持z线所必需的。Cypher是一种z线特异性蛋白质，目前正在准备一份手稿，其中包括高倍电子显微镜断层扫描。Cypher的六个同工型可以根据包含的骨骼或心脏特定结构域分为骨骼或心脏特定类。短异构体和长异构体共享一个n端PDZ结构域，但三个c端LIM结构域是长异构体所特有的。为了研究剪接变异在体内的功能，我们通过用编码短或长骨骼肌同种异构体的cdna替换内源性Cypher基因，对Cypher零突变体进行了修复实验。与Cypher缺失小鼠相比，只表达短或长骨骼肌特定亚型的小鼠中有一定比例的小鼠可以存活至少一年。尽管存活的小鼠表现出肌肉病理，但这些结果表明，任何一种同种异构体都足以挽救与Cypher缺失相关的致死率。