Duchenne muscular dystrophy (DMD) is the second most common fatal genetic disease in humans and is characterized by the absence of a functional copy of the protein dystrophin from skeletal muscle. In dystrophin-negative humans and rodents, regenerated skeletal muscle fibers show abnormal branching. The number of fibers with branches and the complexity of branching increases with each cycle of degeneration/regeneration. Previously, using the mdx mouse model of DMD, we have proposed that once the number and complexity of branched fibers present in dystrophic fast-twitch EDL muscle surpasses a stable level, we term "tipping point" the branches, in and of themselves, mechanically weaken the muscle by rupturing when subjected to high forces during eccentric contractions. Here we use the slow-twitch soleus muscle from the dystrophic mdx mouse to study pre-diseased "peri-ambulatory" dystrophic at 2-3 weeks, the peak regenerative "adult" phase at 6-9 weeks and "old" at 58-112 weeks. Using isolated mdx soleus muscles we examined contractile function and response to eccentric contraction correlated with amount and complexity of regenerated branched fibers. The intact muscle was enzymatically dispersed into individual fibers in order to count fiber branching and some muscles were optically cleared to allow laser scanning confocal microscopy. We demonstrate throughout the lifespan of the mdx mouse dystrophic slow-twitch soleus muscle is no more susceptible to eccentric contraction induced injury than age matched littermate controls and that this is correlated with a reduction in the number and complexity of branched fibers compared to fast-twitch dystrophic EDL muscles.

中文翻译：

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在 mdx 小鼠的整个生命周期中，肌营养不良蛋白阴性的慢肌比目鱼肌不易受到离心收缩引起的损伤

Duchenne 肌营养不良症 (DMD) 是人类第二大最常见的致命遗传疾病，其特征是缺乏来自骨骼肌的蛋白质肌营养不良蛋白的功能性副本。在抗肌萎缩蛋白阴性的人类和啮齿动物中，再生的骨骼肌纤维显示异常分支。具有分支的纤维数量和分支的复杂性随着退化/再生的每个循环而增加。以前，使用 DMD 的 mdx 小鼠模型，我们提出，一旦营养不良的快肌 EDL 肌肉中存在的分支纤维的数量和复杂性超过稳定水平，我们就机械地将分支称为“临界点”在离心收缩期间受到很大的力量时，通过破裂来削弱肌肉。在这里，我们使用来自营养不良 mdx 小鼠的慢抽搐比目鱼肌来研究 2-3 周时患病前的“行走周围”营养不良、6-9 周时的峰值再生“成人”阶段和 58 周时的“老”阶段。 112 周。我们使用孤立的 mdx 比目鱼肌检查了收缩功能和对与再生分支纤维的数量和复杂性相关的离心收缩的反应。完整的肌肉被酶促分散到单个纤维中以计算纤维分支，并且一些肌肉被光学清除以允许激光扫描共聚焦显微镜检查。