Targeted deletion of the muscular dystrophy gene myotilin does not perturb muscle structure or function in mice
Targeted deletion of the muscular dystrophy gene myotilin does not perturb muscle structure or function in mice
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DOI：
10.1128/mcb.00561-06
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发表时间：
2007-01-01
影响因子：
5.3
通讯作者：
Carpen, Olli
中科院分区：
文献类型：
--
作者：
Moza, Monica;Mologni, Luca;Carpen, Olli
肌球蛋白，palladin，和myopalladin形成一个新的小亚家族的细胞骨架蛋白，含有免疫球蛋白样结构域。肌动素是一种位于骨骼肌和心肌细胞Z盘的薄的免疫相关蛋白。肌球蛋白与F-肌动蛋白的直接结合、肌动蛋白丝的有效交联以及防止诱导的丝的解体是肌球蛋白的关键作用，其被认为参与肌节的结构维持和功能。肌球蛋白编码基因中的错义突变导致显性肢带型肌营养不良1A型和球体肌病，并且是可导致肌胫肌病的分子缺陷。在这里，我们描述了缺乏肌球蛋白的小鼠，myo（-/-）小鼠的产生和分析。令人惊讶的是，myo（-/-）小鼠保持正常的肌肉肌节和肌膜完整性。此外，肌球蛋白的丢失不会导致新生或成年myo（-/-）小鼠的心脏或其他器官发生变化。这些小鼠发育正常，寿命正常，即使在长期的身体压力下，它们的肌肉能力也与野生型小鼠没有显著差异。结果表明，要么myotilin不参与肌肉发育和基础功能的维持或其他蛋白质作为结构和功能的补偿分子时myotilin缺乏。
Myotilin, palladin, and myopalladin form a novel small subfamily of cytoskeletal proteins that contain immunoglobulin-like domains. Myotilin is a thin filament-associated protein localized at the Z-disk of skeletal and cardiac muscle cells. The direct binding to F-actin, efficient cross-linking of actin filaments, and prevention of induced disassembly of filaments are key roles of myotilin that are thought to be involved in structural maintenance and function of the sarcomere. Missense mutations in the myotilin-encoding gene cause dominant limb girdle muscular dystrophy type 1A and spheroid body myopathy and are the molecular defect that can cause myotibrillar myopathy. Here we describe the generation and analysis of mice that lack myotilin, myo(-/-) mice. Surprisingly, myo(-/-) mice maintain normal muscle sarcomeric and sarcolemmal integrity. Also, loss of myotilin does not cause alterations in the heart or other organs of newborn or adult myo(-/-) mice. The mice develop normally and have a normal life span, and their muscle capacity does not significantly differ from wild-type mice even after prolonged physical stress. The results suggest that either myotilin does not participate in muscle development and basal function maintenance or other proteins serve as structural and functional compensatory molecules when myotilin is absent.