Duchenne muscular dystrophy (DMD) is a X-linked genetic disorder characterized by progressive muscle degeneration caused by DMD gene mutations leading to the absence of dystrophin in the muscle membrane. The clinical course of human DMD is severe, with gradual inability to walk and premature death due to respiratory and cardiac failure. Although rodent and dog models have been useful to study DMD pathogenesis, new models that better recapitulate human DMD are needed to identify efficacious therapies. A new study in Communications Biology reports the development of a microminipig-based DMD model targeting the DMD gene, using the CRISPR/Cas9 system. The DMD microminipigs exhibited key features of human DMD, including early-onset skeletal muscle weakness, reduced locomotion, elevated serum creatine kinase levels, cardiac pathology and sudden death from respiratory failure. The DMD microminipigs, which survived longer (up to 29.9 months) and are easier to handle than previous bigger pig models of DMD, could be a valuable tool for advancing DMD research.

Original reference: Otake, M. et al. Commun. Biol. 7, 523 (2024)

杜氏肌营养不良症 (DMD) 是一种 X 连锁遗传性疾病，其特征是DMD基因突变导致肌膜中缺乏肌营养不良蛋白，导致进行性肌肉退化。人类DMD的临床病程很严重，逐渐无法行走，并因呼吸和心力衰竭而过早死亡。尽管啮齿动物和狗模型可用于研究 DMD 发病机制，但需要更好地重现人类 DMD 的新模型来确定有效的治疗方法。 Communications Biology的一项新研究报告了使用 CRISPR/Cas9 系统开发出一种基于微型猪的 DMD 模型，该模型针对DMD基因。 DMD 微型猪表现出人类 DMD 的关键特征，包括早发性骨骼肌无力、运动能力下降、血清肌酸激酶水平升高、心脏病和因呼吸衰竭而猝死。与之前较大的 DMD 猪模型相比，DMD 微型猪的存活时间更长（长达 29.9 个月）并且更容易处理，可能成为推进 DMD 研究的宝贵工具。

原始参考文献： Otake, M. et al .交流。生物。 7 , 523 (2024)