Dystrophin, encoded by the DMD gene on the X chromosome, stabilizes the sarcolemma by linking the actin cytoskeleton with the dystrophin-glycoprotein complex (DGC). In-frame mutations in DMD cause a milder form of X-linked muscular dystrophy, called Becker muscular dystrophy (BMD), characterized by the reduced expression of truncated dystrophin. So far, no animal model with in-frame mutations in Dmd has been established. As a result, the effect of in-frame mutations on the dystrophin expression profile and disease progression of BMD remains unclear. In this study, we established a novel rat model carrying in-frame Dmd gene mutations (IF rats) and evaluated the pathology. We found that IF rats exhibit reduced expression of truncated dystrophin in a proteasome-independent manner. This abnormal dystrophin expression caused dystrophic changes in muscle tissues, but did not lead to functional deficiency. We also found that the expression of additional dystrophin named dpX, which forms the DGC in the sarcolemma, is associated with the appearance of truncated dystrophin. In conclusion, the outcomes of this study contribute to the further understanding of BMD pathology and help elucidate the efficiency of dystrophin recovery treatments in Duchenne muscular dystrophy, a more severe form of X-linked muscular dystrophy.

中文翻译：

---

携带肌营养不良蛋白基因框内突变的大鼠的病理学评估：贝克型肌营养不良症的新模型。

肌营养不良蛋白由X 染色体上的DMD基因编码，通过将肌动蛋白细胞骨架与肌营养不良蛋白-糖蛋白复合物 (DGC) 连接来稳定肌膜。DMD的框内突变会导致一种较温和的 X 连锁肌营养不良症，称为贝克尔肌营养不良症 (BMD)，其特征是截短肌营养不良蛋白的表达减少。迄今为止，尚未建立Dmd框内突变的动物模型。因此，框内突变对肌营养不良蛋白表达谱和 BMD 疾病进展的影响仍不清楚。在本研究中，我们建立了一种携带框内Dmd基因突变的新型大鼠模型（IF 大鼠）并评估了病理学。我们发现 IF 大鼠以不依赖于蛋白酶体的方式表现出截短肌营养不良蛋白的表达减少。这种异常的肌营养不良蛋白表达导致了肌肉组织的营养不良变化，但并没有导致功能缺陷。我们还发现，肌营养不良蛋白 dpX 的表达与截短的肌营养不良蛋白的出现有关，它在肌膜中形成 DGC。总之，这项研究的结果有助于进一步了解 BMD 病理学，并有助于阐明肌营养不良蛋白恢复治疗杜氏肌营养不良症（一种更严重的 X 连锁肌营养不良症）的有效性。