Lack of myostatin results in excessive muscle growth but impaired force generation
Lack of myostatin results in excessive muscle growth but impaired force generation
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DOI：
10.1073/pnas.0604893104
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发表时间：
2007-02-06
影响因子：
11.1
通讯作者：
Patel, Ketan
中科院分区：
文献类型：
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作者：
Amthor, Helge;Macharia, Raymond;Patel, Ketan
肌生长抑制素的缺乏促进骨骼肌的生长，并且已经提出阻断其活性作为各种肌肉消耗性疾病的治疗。在这里，我们已经检查了两个独立的小鼠品系，其在肌生长抑制素基因中具有突变，组成型无效（MSTO（-/-））和紧凑型（柏林高线，BEHc/c）。我们报告说，尽管相对于年龄匹配的野生型有更大的肌肉质量，但最大强直力产生没有增加，但当表达为肌肉大小（比力）的函数时，肌肉生长抑制素缺陷小鼠的肌肉比野生型肌肉弱。此外，在单次抽搐过程中，MIPs（-/-）肌肉收缩和放松速度更快，并且相对于野生型对照组，IIb型纤维的数量显著增加。这种变化也伴随着一个显着增加IIB型纤维含有管状聚集体。此外，线粒体DNA与核DNA的比率和线粒体数量在肌生长抑制素缺乏的肌肉中减少，表明线粒体耗竭。总的来说，我们的研究结果表明，缺乏肌肉生长抑制素的影响力的生产与骨骼肌的氧化特性的损失。
The lack of myostatin promotes growth of skeletal muscle, and blockade of its activity has been proposed as a treatment for various muscle-wasting disorders. Here, we have examined two independent mouse lines that harbor mutations in the myostatin gene, constitutive null (Mstn(-/-)) and compact (Berlin High Line, BEHc/c). We report that, despite a larger muscle mass relative to age-matched wild types, there was no increase in maximum tetanic force generation, but that when expressed as a function of muscle size (specific force), muscles of myostatin-deficient mice were weaker than wild-type muscles. In addition, Mstn(-/-) muscle contracted and relaxed faster during a single twitch and had a marked increase in the number of type IIb fibers relative to wild-type controls. This change was also accompanied by a significant increase in type IIB fibers containing tubular aggregates. Moreover, the ratio of mitochondrial DNA to nuclear DNA and mitochondria number were decreased in myostatin-deficient muscle, suggesting a mitochondrial depletion. Overall, our results suggest that lack of myostatin compromises force production in association with loss of oxidative characteristics of skeletal muscle.