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. Although 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 Δ52-54). The Dmd Δ52-54 mutation led to the absence of dystrophin, resulting in progressive muscle deterioration with weakened muscle strength. Moreover, Dmd Δ52-54 mice present with early-onset hypertrophic cardiomyopathy, which is absent in current pre-clinical dystrophin-deficient mouse models. Therefore, Dmd Δ52-54 presents itself as an excellent pre-clinical model to evaluate the impact on skeletal and cardiac muscles for both mutation-dependent and -independent approaches.

中文翻译：

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一种携带多外显子 Dmd 缺失的杜氏肌营养不良症的新型小鼠模型表现出进行性肌营养不良症和早发性心肌病。

Duchenne 肌营养不良症 (DMD) 是一种危及生命的神经肌肉疾病，由缺乏肌营养不良蛋白引起，导致进行性肌肉萎缩和运动功能障碍。到成年，几乎所有患者都会患上心肌病，这是 DMD 死亡的主要原因。尽管在创建动物模型以研究 DMD 的治疗策略方面付出了大量努力，但大多数都未能概括受影响患者的完整骨骼和心脏疾病表现。在这里，我们生成了一个小鼠模型，反映了外显子 52-54 ( Dmd Δ52-54 )的患者缺失突变。所述DMDΔ52-54突变导致缺少抗肌萎缩蛋白，导致与弱化肌肉强度渐进性肌肉退化。此外，Dmd Δ52-54小鼠出现早发性肥厚性心肌病，这在目前的临床前肌营养不良蛋白缺陷小鼠模型中是不存在的。因此，Dmd Δ52-54是一种出色的临床前模型，可评估突变依赖和独立方法对骨骼肌和心肌的影响。