Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Methods Mol Biol. 2020;2105:241-250. doi: 10.1007/978-1-0716-0243-0_15.
Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy and is caused by gene mutations that abolish production of functional dystrophin muscle protein. A promising new treatment exploits specifically targeted RNA-acting drugs that are able to partially restore the dystrophin protein. The mdx mouse model (animal model of DMD) serves as a good in vivo model for testing these antisense drugs. The simplest in vivo test, which circumvents the systemic circulation, is intramuscular administration of the compound. After 7 days it is possible to detect exon skipping by reverse transcriptase PCR, and newly synthesized dystrophin-positive fibers by immunohistochemistry and western blotting. All muscles, including the heart, are affected by the disease and must be treated. Therefore the use of antisense therapy for treatment of DMD requires systemic administration, and the model is also useful for systemic administration.
杜氏肌营养不良症（DMD）是最常见和最严重的肌肉营养不良症，是由基因突变为肌肉蛋白产生功能性肌营养不良蛋白而引起的。一种很有前途的新治疗方法利用了专门靶向 RNA 的药物，这些药物能够部分恢复肌营养不良蛋白。mdx 小鼠模型（DMD 的动物模型）是测试这些反义药物的良好体内模型。最简单的体内测试是绕过全身循环的肌肉内给药。7 天后，可以通过逆转录 PCR 检测外显子跳跃，通过免疫组织化学和 Western blot 检测新合成的肌营养不良蛋白阳性纤维。所有肌肉，包括心脏，都受到疾病的影响，必须进行治疗。因此，反义疗法治疗 DMD 需要全身给药，该模型对全身给药也很有用。
