J Neuromuscul Dis. 2023;10(6):1003-1012. doi: 10.3233/JND-230126.
Duchenne muscular dystrophy (DMD) is a severe form of muscular dystrophy (MD) that is characterized by early muscle wasting and lethal cardiorespiratory failure. While the mdx mouse is the most common model of DMD, it fails to replicate the severe loss of muscle mass and other complications observed in patients, in part due to the multiple rescue pathways found in mice. This led to several attempts at improving DMD animal models by interfering with these rescue pathways through double transgenic approaches, resulting in more severe phenotypes with mixed relevance to the human pathology. As a growing body of literature depicts DMD as a multi-system metabolic disease, improvements in mdx-based modeling of DMD may be achieved by modulating whole-body metabolism instead of muscle homeostasis. This review provides an overview of the established dual-transgenic approaches that exacerbate the mild mdx phenotype by primarily interfering with muscle homeostasis and highlights how advances in DMD modeling coincide with inducing whole-body metabolic changes. We focus on the DBA2/J strain-based D2.mdx mouse with heightened transforming growth factor (TGF)-β signaling and the dyslipidemic mdx/apolipoprotein E (mdx/ApoE) knock-out (KO) mouse, and summarize how these novel models emulate the metabolic changes observed in DMD.
杜氏肌营养不良症（DMD）是一种严重的肌肉营养不良症（MD），其特征是早期肌肉萎缩和致命的心肺衰竭。虽然 mdx 小鼠是 DMD 最常见的模型，但它无法复制患者中观察到的严重肌肉质量损失和其他并发症，部分原因是在小鼠中发现了多种挽救途径。这导致了通过双转基因方法干扰这些挽救途径来改进 DMD 动物模型的几次尝试，导致与人类病理学相关性混合的更严重表型。随着越来越多的文献将 DMD 描述为一种多系统代谢疾病，通过调节全身代谢而不是肌肉内稳态来改善基于 mdx 的 DMD 模型可能成为可能。这篇综述概述了通过主要干扰肌肉内稳态来加重轻度 mdx 表型的既定双转基因方法，并强调了 DMD 建模的进展如何与诱导全身代谢变化相一致。我们专注于具有增强的转化生长因子（TGF）-β信号的 DBA2/J 品系 D2.mdx 小鼠和血脂异常的 mdx/载脂蛋白 E（mdx/ApoE）敲除（KO）小鼠，并总结了这些新型模型如何模拟 DMD 中观察到的代谢变化。
