Skeletal and cardiac myopathies in mice lacking utrophin and dystrophin: A model for Duchenne muscular dystrophy
Skeletal and cardiac myopathies in mice lacking utrophin and dystrophin: A model for Duchenne muscular dystrophy
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DOI：
10.1016/s0092-8674(00)80533-4
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发表时间：
1997-08-22
期刊：
影响因子：
64.5
通讯作者：
Sanes, JR
中科院分区：
文献类型：
--
作者：
Grady, RM;Teng, HB;Sanes, JR
肌营养不良蛋白是一种肌肉纤维的细胞骨架蛋白；在人类中，它的抛出会导致杜氏肌营养不良症，不可避免地会造成骨骼肌和心肌的致命损耗。MDX小鼠也缺乏营养不良蛋白，但只是轻度营养不良。Utroin是dystrophin的同系物，局限于骨骼神经肌肉接头处的突触后膜上，与突触发育有关。然而，缺乏utroin的小鼠只表现出轻微的神经肌肉缺陷。在这里，我们询问两个单一突变体的温和表型是否反映了两种蛋白质之间的补偿。双突变体的突触发育在质量上是正常的，但营养不良很严重，与杜兴的情况非常相似。因此，utroin可以减轻dystrophin缺乏症的影响，该双突变体可能为研究其发病机制和治疗提供了一个有用的模型。
Dystrophin is a cytoskeletal protein of muscle fibers; its toss in humans leads to Duchenne muscular dystrophy, an inevitably fatal wasting of skeletal and cardiac muscle. mdx mice also lack dystrophin, but are only mildly dystrophic. Utrophin, a homolog of dystrophin, is confined to the postsynaptic membrane at skeletal neuromuscular junctions and has been implicated in synaptic development. However, mice lacking utrophin show only subtle neuromuscular defects. Here, we asked whether the mild phenotypes of the two single mutants reflect compensation between the two proteins. Synaptic development was qualitatively normal in double mutants, but dystrophy was severe and closely resembled that seen in Duchenne. Thus, utrophin attenuates the effects of dystrophin deficiency, and the double mutant may provide a useful model for studies of pathogenesis and therapy.