Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy
Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy
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DOI：
10.1016/s0092-8674(00)80532-2
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发表时间：
1997-08-22
期刊：
影响因子：
64.5
通讯作者：
Davies, KE
中科院分区：
文献类型：
--
作者：
Deconinck, AE;Rafael, JA;Davies, KE
肌膜缺乏抗肌萎缩蛋白导致杜氏肌营养不良症（DMD），这是一种严重的肌肉萎缩性疾病，在成年早期不可避免地致命。相比之下，肌营养不良蛋白缺陷mdx小鼠的身体表现正常，尽管其潜在的肌肉病理。我们描述了小鼠缺乏肌营养不良蛋白和肌营养不良蛋白相关蛋白utrophin。这些小鼠表现出许多人类DMD的典型体征：它们表现出导致过早死亡的严重进行性肌营养不良，它们具有超微结构神经肌肉和肌腱接头异常，并且它们在纤维内异常共表达肌球蛋白重链同种型。这些数据表明，肌营养不良蛋白和肌营养不良蛋白在肌肉的正常功能或发育途径中具有互补作用。对这些小鼠的详细研究将为DMD的发病机制提供新的见解，并为快速评估基因治疗策略提供改进的模型。
The absence of dystrophin at the muscle membrane leads to Duchenne muscular dystrophy (DMD), a severe muscle-wasting disease that is inevitably fatal in early adulthood. In contrast, dystrophin-deficient mdx mice appear physically normal despite their underlying muscle pathology. We describe mice deficient for both dystrophin and the dystrophin-related protein utrophin. These mice show many signs typical of DMD in humans: they show severe progressive muscular dystrophy that results in premature death, they have ultrastructural neuromuscular and myotendinous junction abnormalities, and they aberrantly coexpress myosin heavy chain isoforms within a fiber. The data suggest that utrophin and dystrophin have complementing roles in normal functional or developmental pathways in muscle. Detailed study of these mice should provide novel insights into the pathogenesis of DMD and provide an improved model for rapid evaluation of gene therapy strategies.