Absence of heartbeat in the Xenopus tropicalis mutation muzak is caused by a nonsense mutation in cardiac myosin myh6
Absence of heartbeat in the Xenopus tropicalis mutation muzak is caused by a nonsense mutation in cardiac myosin myh6
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DOI：
10.1016/j.ydbio.2009.09.019
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发表时间：
2009-12-01
影响因子：
2.7
通讯作者：
Zimmerman, Lyle B.
中科院分区：
文献类型：
--
作者：
Abu-Daya, Anita;Sater, Amy K.;Zimmerman, Lyle B.
耦合心脏功能和心脏形态发生的机制可以在低等脊椎动物胚胎中获得，这些胚胎可以在扩散氧下存活到游泳蝌蚪阶段。热带爪蟾的正向遗传筛选已经确定了80多个影响不同发育过程的突变，包括心脏形态发生和功能。在第一个位置克隆的突变在热带爪蟾，我们表明，非收缩性心脏muzak（muz）胚胎是由一个过早的终止密码子在心脏肌球蛋白重链基因myh6。这种突变删除了负责聚合成粗丝的卷曲螺旋结构域，严重破坏了心肌细胞的细胞骨架。尽管缺乏收缩活动和缺乏主要结构蛋白，但心脏形态发生的早期阶段，包括成环和腔室形成是非常正常的。Muz心脏随后发展为扩张的腔室，具有压缩的内膜，并且不能形成可识别的心脏瓣膜和小梁。(C)2009 Elsevier Inc. All rights reserved.
Mechanisms coupling heart function and cardiac morphogenesis can be accessed in lower vertebrate embryos that can survive to swimming tadpole stages on diffused oxygen. Forward genetic screens in Xenopus tropicalis have identified more than 80 mutations affecting diverse developmental processes, including cardiac morphogenesis and function. In the first positional cloning of a mutation in X tropicalis, we show that non-contractile hearts in muzak (muz) embryos are caused by a premature stop codon in the cardiac myosin heavy chain gene myh6. The mutation deletes the coiled-coil domain responsible for polymerization into thick filaments, severely disrupting the cardiomyocyte cytoskeleton. Despite the lack of contractile activity and absence of a major structural protein, early stages of cardiac morphogenesis including looping and chamber formation are grossly normal. Muz hearts subsequently develop dilated chambers with compressed endocardium and fail to form identifiable cardiac valves and trabeculae. (C) 2009 Elsevier Inc. All rights reserved.