Pathological alterations in the gastrointestinal tract of a porcine model of DMD.
Pathological alterations in the gastrointestinal tract of a porcine model of DMD.
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DOI：
10.1186/s13578-021-00647-9
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发表时间：
2021-07-15
影响因子：
7.5
通讯作者：
Tang X
中科院分区：
文献类型：
--
作者：
Zou X;Ouyang H;Pang D;Han R;Tang X
杜氏肌营养不良症（DMD）患者会出现严重的骨骼和心肌病变，导致过早死亡。因此，目前的治疗努力主要针对纠正骨骼肌和心脏中的肌营养不良蛋白表达。然而，据报道，DMD患者也可能表现出胃肠道和营养问题。胃肠道组织的病理学改变如何导致这种疾病还没有完全探讨。本研究采用CRISPR/Cas9系统结合体细胞核移植技术（SCNT）建立猪DMD模型，并探讨其病理变化。我们发现，基因干扰dystrophin的表达，导致形态学的胃肠道改变，削弱胃肠道消化和吸收能力，并最终导致营养不良和胃功能障碍的DMD猪。这项工作提供了重要的见解DMD的发病机制，并强调需要考虑作为一个额外的治疗目标DMD患者的胃肠道功能障碍。在线版本包含补充材料，可通过10.1186/s13578-021-00647-9获得。
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. The online version contains supplementary material available at 10.1186/s13578-021-00647-9.
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