Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
PLoS One. 2011 Jan 14;6(1):e16184. doi: 10.1371/journal.pone.0016184.
Duchenne muscular dystrophy (DMD) is the most prevalent inherited childhood muscle disorder in humans. mdx mice exhibit a similar pathophysiology to the human disorder allowing for an in-depth investigation of DMD. Myogenin, a myogenic regulatory factor, is best known for its role in embryonic myogenesis, but its role in adult muscle maintenance and regeneration is still poorly understood. Here, we generated an mdx:Myog(flox/flox) mouse harboring a tamoxifen-inducible Cre recombinase transgene, which was used to conditionally delete Myog during adult life. After tamoxifen treatment, three groups of mice were created to study the effects of Myog deletion: mdx:Myog(flox/flox) mice (mdx), Myog(flox/flox) mice (wild-type), and mdx:Myog(floxΔ/floxΔ):Cre-ER mice (mdx:Myog-deleted). mdx:Myog-deleted mice exhibited no adverse phenotype and behaved normally. When run to exhaustion, mdx:Myog-deleted mice demonstrated an enhanced capacity for exercise compared to mdx mice, running nearly as far as wild-type mice. Moreover, these mice showed the same signature characteristics of muscle regeneration as mdx mice. Unexpectedly, we found that myogenin was dispensable for muscle regeneration. Factors associated with muscle fatigue, metabolism, and proteolysis were significantly altered in mdx:Myog-deleted mice, and this might contribute to their increased exercise capacity. Our results reveal novel functions for myogenin in adult muscle and suggest that reducing Myog expression in other muscle disease models may partially restore muscle function.
杜氏肌营养不良症（DMD）是人类最常见的遗传性儿童肌肉疾病。mdx 小鼠表现出与人类疾病相似的病理生理学特征，允许对 DMD 进行深入研究。肌生成素（Myogenin）是一种肌肉调节因子，最著名的是其在胚胎肌发生中的作用，但它在成年肌肉维持和再生中的作用仍知之甚少。在这里，我们生成了一种 mdx：Myog（flox/flox）小鼠，其携带一种可诱导型 Cre 重组酶转基因，该基因可在成年期条件性删除 Myog。在用他莫昔芬处理后，创建了三组小鼠来研究 Myog 缺失的影响：mdx：Myog（flox/flox）小鼠（mdx）、Myog（flox/flox）小鼠（野生型）和 mdx：Myog（floxΔ/floxΔ）：Cre-ER 小鼠（mdx：Myog 缺失）。mdx：Myog 缺失的小鼠没有表现出不良表型，行为正常。当耗尽时，mdx：Myog 缺失的小鼠在运动能力上表现出增强的能力，与 mdx 小鼠相比，它们几乎可以跑与野生型小鼠一样远。此外，这些小鼠表现出与 mdx 小鼠相同的肌肉再生特征。出乎意料的是，我们发现肌生成素对于肌肉再生是可有可无的。与肌肉疲劳、代谢和蛋白水解相关的因素在 mdx：Myog 缺失的小鼠中发生了显著改变，这可能有助于它们提高运动能力。我们的结果揭示了肌生成素在成年肌肉中的新功能，并表明在其他肌肉疾病模型中降低 Myog 表达可能会部分恢复肌肉功能。
