Cypher and Enigma homolog protein are essential for cardiac development and embryonic survival.
Cypher and Enigma homolog protein are essential for cardiac development and embryonic survival.
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DOI：
10.1161/jaha.115.001950
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发表时间：
2015-05-05
影响因子：
5.4
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Mu Y;Jing R;Peter AK;Lange S;Lin L;Zhang J;Ouyang K;Fang X;Veevers J;Zhou X;Evans SM;Cheng H;Chen J
横纹肌Z线是位于肌节之间的多蛋白复合物，在维持横纹肌结构和功能方面起着不可或缺的作用。多种Z线相关蛋白已被鉴定并显示在人类心肌病的发病机制中发挥越来越重要的作用。Cypher及其同源蛋白Enigma homolog protein（ENH）是两种Z线蛋白，它们分别对出生后心脏功能的维持和肌肉收缩时Z线的稳定性起重要作用，但对心肌原纤维的发生和发育起重要作用。目前的研究旨在测试Cypher和ENH是否在胚胎发育过程中发挥多余的作用。在这里，我们证明了缺乏ENH和Cypher的小鼠表现出胚胎致死和生长迟缓。双基因敲除胚胎的致死率与心脏扩张和Z线结构异常有关。此外，当ENH与Cypher短亚型（CypherS）或Cypher长亚型（CypherL）的选择性消融结合时，只有后者导致胚胎致死。Cypher和ENH从心脏功能的最早阶段起在维持Z线结构中起着重要作用，并且是维持正常胚胎心脏功能和胚胎存活力所必需的。
The striated muscle Z-line, a multiprotein complex at the boundary between sarcomeres, plays an integral role in maintaining striated muscle structure and function. Multiple Z-line-associated proteins have been identified and shown to play an increasingly important role in the pathogenesis of human cardiomyopathy. Cypher and its close homologue, Enigma homolog protein (ENH), are 2 Z-line proteins previously shown to be individually essential for maintenance of postnatal cardiac function and stability of the Z-line during muscle contraction, but dispensable for cardiac myofibrillogenesis and development. The current studies were designed to test whether Cypher and ENH play redundant roles during embryonic development. Here, we demonstrated that mice lacking both ENH and Cypher exhibited embryonic lethality and growth retardation. Lethality in double knockout embryos was associated with cardiac dilation and abnormal Z-line structure. In addition, when ENH was ablated in conjunction with selective ablation of either Cypher short isoforms (CypherS), or Cypher long isoforms (CypherL), only the latter resulted in embryonic lethality. Cypher and ENH redundantly play an essential role in sustaining Z-line structure from the earliest stages of cardiac function, and are redundantly required to maintain normal embryonic heart function and embryonic viability.