The absence of dystrophin rather than muscle degeneration causes acetylcholine receptor cluster defects in dystrophic muscle
The absence of dystrophin rather than muscle degeneration causes acetylcholine receptor cluster defects in dystrophic muscle
复制标题
肌营养不良蛋白的缺失而不是肌肉退化导致肌营养不良的乙酰胆碱受体簇缺陷
DOI：
10.1097/wnr.0b013e32834e7e54
复制
发表时间：
2012-01-25
期刊：
影响因子：
1.7
通讯作者：
Zhang, Cheng
中科院分区：
文献类型：
--
作者：
Kong, Jie;Yang, Liqing;Zhang, Cheng
杜氏肌营养不良症是最常见的遗传性肌肉疾病。受影响的肌肉以乙酰胆碱受体（AChR）聚集异常为特征。一些研究表明，AChR簇的变化继发于退行性过程。在这项研究中，我们证明了AChR簇断裂和肌肉退变是独立的事件。我们比较了mdx小鼠（突变的肌营养不良蛋白）和dko小鼠（突变的肌营养不良蛋白和肌营养不良蛋白）的AChR簇和病理特征。通过与&agr结合鉴定AChR簇；经经典免疫组织化学技术观察病理特征。mdx和dko小鼠的AChR簇数量减少，结构断裂。然而，mdx和dko小鼠的AChR簇裂性没有显著差异，尽管dko小鼠的炎症浸润和变性更为严重。此外，在mdx和dko小鼠中，与肌营养不良蛋白相互作用并将自身固定在肌膜上的神经元一氧化氮合酶明显减少。AChR的断裂和肌肉退行性变是不同的事件，两者都是肌膜和细胞骨架不稳定的继发性结果。
Duchenne muscular dystrophy is the most common genetic muscle disease. Affected muscles are characterized by abnormal acetylcholine receptor (AChR) clustering. Some studies have suggested that changes in AChR clusters are secondary to degenerative processes. In this study, we demonstrate that AChR cluster fragmentation and muscle degeneration are separate events. We compared AChR clusters and pathological features in mdx mice (mutated dystrophin) and dko mice (mutated dystrophin and utrophin). AChR clusters were identified by binding with &agr;-bungarotoxin, and pathological features were observed by classical immunohistochemical techniques. AChR clusters in mdx and dko mice were reduced in number and exhibited structural fragmentation. However, AChR cluster fragmentation was not significantly different in mdx and dko mice, although more severe inflammatory infiltration and degeneration were observed in dko mice. Furthermore, neuronal nitric oxide synthase, which interacts with dystrophin to anchor itself at the sarcolemma, was notably reduced in mdx and dko mice. Fragmentation of AChR and muscle degeneration are separate events, and both are secondary results of destabilization on the sarcolemma and the cytoskeleton.