Law D J, Tidball J G
Department of Physiological Science, University of California, Los Angeles 90024-1527.
Am J Pathol. 1993 May;142(5):1513-23.
The myotendinous junction (MTJ) is the major site of force transmission from myofibrils across the muscle cell membrane to the extracellular matrix. The MTJ is thus an appropriate model system in which to test the hypothesis that dystrophin, the gene product absent in Duchenne muscular dystrophy, functions as a structural link between the muscle cytoskeleton and the cell membrane. We studied changes in MTJ structure in dystrophin-deficient mdx mice during periods of growth and aging that spanned prenecrotic, necrotic, and regenerative phases of postnatal muscle development in mdx mice. Prenecrotic animals were found to exhibit structural defects at MTJs that were similar to those described previously in animals at the peak of necrosis, including a reduction in lateral associations between thin filaments and the MTJ membrane. These defects therefore occur before necrosis and may be directly related to the absence of dystrophin. Observations of regenerating and fully regenerated MTJs in adult animals show that the defects are still present, indicating that normal thin filament-membrane associations are never formed in dystrophin-deficient muscle. However, in prenecrotic as well as regenerated adult mdx muscle, the MTJ membrane is only slightly less folded than in age-matched controls. This indicates that mdx muscle possesses some dystrophin-independent mechanism that allows for the initial formation of MTJs, despite the absence of dystrophin. The presence of the defect in normal, lateral, thin filament-membrane associations in mdx muscle, regardless of age, supports the hypothesis that dystrophin functions as a structural link between thin filaments and the membrane.
肌-腱连接点（MTJ）是力量从肌原纤维穿过肌细胞膜传递至细胞外基质的主要部位。因此，MTJ是一个合适的模型系统，可用于检验如下假说：杜兴氏肌营养不良症中缺失的基因产物抗肌萎缩蛋白，作为肌肉细胞骨架与细胞膜之间的结构连接发挥作用。我们研究了抗肌萎缩蛋白缺陷的mdx小鼠在生长和衰老期间MTJ结构的变化，这一时期涵盖了mdx小鼠出生后肌肉发育的坏死前期、坏死期和再生期。研究发现，坏死前期的动物MTJ处存在结构缺陷，与之前描述的处于坏死高峰期的动物的缺陷相似，包括细肌丝与MTJ膜之间的横向连接减少。因此，这些缺陷在坏死之前就已出现，可能与抗肌萎缩蛋白的缺失直接相关。对成年动物再生和完全再生的MTJ的观察表明，这些缺陷仍然存在，这表明在缺乏抗肌萎缩蛋白的肌肉中从未形成正常的细肌丝-膜连接。然而，在坏死前期以及再生后的成年mdx肌肉中，MTJ膜的折叠程度仅略低于年龄匹配的对照。这表明mdx肌肉拥有一些不依赖抗肌萎缩蛋白的机制，尽管缺乏抗肌萎缩蛋白，但仍能允许MTJ的初始形成。无论年龄如何，mdx肌肉中正常的横向细肌丝-膜连接存在缺陷，这支持了抗肌萎缩蛋白作为细肌丝与膜之间结构连接发挥作用的假说。
