Mitochondrial derangement is an important contributor to the pathophysiology of muscular dystrophies and may be among the earliest cellular deficits. We have previously shown that disruption of Mss51, a mammalian skeletal muscle protein that localizes to the mitochondria, results in enhanced muscle oxygen consumption rate, increased endurance capacity, and improved limb muscle strength in mice with wildtype background. Here, we investigate whether Mss51 deletion in the mdx murine model of Duchenne muscular dystrophy (mdx-Mss51 KO) counteracts the muscle pathology and mitochondrial irregularities observed in mdx mice. We found that mdx-Mss51 KO mice had increased myofiber oxygen consumption rates and an amelioration of muscle histopathology compared to mdx counterparts. This corresponded with greater treadmill endurance and less percent fatigue in muscle physiology, but no improvement in forelimb grip strength or limb muscle force production. These findings suggest that although Mss51 deletion ameliorates the skeletal muscle mitochondrial respiration defects in mdx and improves fatigue resistance in vivo, the lack of improvement in force production suggests that this target alone may be insufficient for a therapeutic effect.

中文翻译：

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Mss51 缺失增加了耐力并改善了杜氏肌营养不良症 mdx 小鼠模型的组织病理学

线粒体紊乱是肌营养不良症病理生理学的重要因素，可能是最早的细胞缺陷之一。我们之前已经表明，破坏 Mss51（一种定位于线粒体的哺乳动物骨骼肌蛋白）会导致具有野生型背景的小鼠的肌肉耗氧率增加、耐力能力增加和肢体肌肉力量改善。在这里，我们研究了杜氏肌营养不良症 (mdx-Mss51 KO) 的 mdx 小鼠模型中的 Mss51 缺失是否抵消了在 mdx 小鼠中观察到的肌肉病理和线粒体异常。我们发现，与 mdx 对应物相比，mdx-Mss51 KO 小鼠增加了肌纤维耗氧率并改善了肌肉组织病理学。这对应于更大的跑步机耐力和更少的肌肉生理疲劳百分比，但前肢握力或四肢肌肉力量的产生没有改善。这些发现表明，虽然 Mss51 缺失改善了 mdx 中的骨骼肌线粒体呼吸缺陷并提高了体内的抗疲劳性，但力产生的缺乏改善表明仅此目标可能不足以产生治疗效果。