Novel DMD mouse model carrying a multi-exonic Dmd deletion exhibit progressive muscular dystrophy and early-onset cardiomyopathy

Duchenne muscular dystrophy (DMD) is a life-threatening neuromuscular disease caused by the lack of dystrophin, resulting in progressive muscle wasting and locomotor dysfunctions. By adulthood, almost all patients also develop cardiomyopathy, which is the primary cause of death in DMD. While there has been extensive effort in creating animal models to study treatment strategies for DMD, most fail to recapitulate the complete skeletal and cardiac disease manifestations that are presented in affected patients. Here, we generated a mouse model mirroring a patient deletion mutation of exons 52-54 (Dmd &[Delta]52-54). The Dmd &[Delta]52-54 mutation led to the absence of dystrophin, resulting in progressive muscle deterioration with weakened muscle strength. Moreover, Dmd &[Delta]52-54 present with early-onset cardiomyopathy which is absent in current pre-clinical dystrophin deficient mouse models. Therefore, Dmd &[Delta]52-54 presents itself as an excellent pre-clinical model...

杜氏肌营养不良症（Duchenne muscular dystrophy, DMD）是一种由 dystrophin 蛋白缺失引发的危及生命的神经肌肉疾病（neuromuscular disease），其特征为进行性肌肉萎缩及运动功能障碍。成年后，几乎所有患者都会并发心肌病（cardiomyopathy），这是DMD患者死亡的主要原因。尽管科研人员已投入大量精力构建DMD治疗策略研究的动物模型，但多数模型无法重现患者身上完整的骨骼肌肉及心脏病变表型。本研究构建了一种模拟患者外显子52-54缺失突变的小鼠模型（Dmd Δ52-54）。Dmd Δ52-54突变导致dystrophin蛋白缺失，引发进行性肌肉退化及肌力减弱。此外，该模型表现出早发性心肌病——这一特征在现有临床前 dystrophin 缺陷小鼠模型中均未出现。因此，Dmd Δ52-54模型是一种优异的临床前研究模型……