Patients with Duchenne muscular dystrophy (DMD) develop severe skeletal and cardiac muscle pathologies, which result in premature death. Therefore, the current therapeutic efforts are mainly targeted to correct dystrophin expression in skeletal muscle and heart. However, it was reported that DMD patients may also exhibit gastrointestinal and nutritional problems. How the pathological alterations in gastrointestinal tissues contribute to the disease are not fully explored. Here we employed the CRISPR/Cas9 system combined with somatic nuclear transfer technology (SCNT) to establish a porcine model of DMD and explored their pathological alterations. We found that genetic disruption of dystrophin expression led to morphological gastrointestinal tract alterations, weakened the gastrointestinal tract digestion and absorption capacity, and eventually led to malnutrition and gastric dysfunction in the DMD pigs. This work provides important insights into the pathogenesis of DMD and highlights the need to consider the gastrointestinal dysfunction as an additional therapeutic target for DMD patients.

中文翻译：

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DMD猪模型胃肠道病理改变

杜氏肌营养不良症 (DMD) 患者会出现严重的骨骼肌和心肌病变，导致过早死亡。因此，目前的治疗工作主要针对纠正骨骼肌和心脏中肌营养不良蛋白的表达。然而，据报道，DMD 患者也可能表现出胃肠道和营养问题。胃肠组织的病理改变如何导致该疾病尚未得到充分探索。在这里，我们采用 CRISPR/Cas9 系统结合体细胞核转移技术 (SCNT) 建立 DMD 的猪模型并探索其病理改变。我们发现抗肌萎缩蛋白表达的遗传破坏导致胃肠道形态学改变，削弱胃肠道消化吸收能力，并最终导致 DMD 猪营养不良和胃功能障碍。这项工作提供了对 DMD 发病机制的重要见解，并强调需要考虑将胃肠功能障碍作为 DMD 患者的额外治疗靶点。