Transcriptomic profiles of muscular dystrophy with myositis (mdm) in extensor digitorum longus, psoas, and soleus muscles from mice

Titinopathies are inherited muscular diseases triggered by genetic mutations in the titin gene. Muscular dystrophy with myositis (mdm) is one such disease caused by a deletion in the N2A-PEVK region of titin, one of the most active binding sites in titin, and mice with this deletion develop progressive muscle degeneration. The range of phenotypic differences observed in mdm mice extends well beyond impacts on titin, making it clear that deletion of this region initiates a cascade of additional transcriptomic changes. Previous research has focused on correlating phenotypic differences with muscle function in mdm mice. These studies have provided understanding of the downstream physiological effects resulting from the deletion but only provide insights on processes that can be physiologically observed and measured. We used differential gene expression (DGE) to compare the transcriptomes of extensor digitorum longus (EDL), psoas and soleus muscles from wild-type and mdm mice to develop a deeper understand of these tissue-specific responses. Comparative study of transcriptomes of slow-twitch Soleus and fast-twitch TA muscle tissues.肌联蛋白病（Titinopathies）是一类由肌联蛋白（titin）基因的遗传突变诱发的遗传性肌肉疾病。伴肌炎的肌营养不良症（mdm）便是其中一例，其病因是肌联蛋白N2A-PEVK区域的缺失——该区域是肌联蛋白中活性最高的结合位点之一；携带该缺失的小鼠会出现进行性肌肉变性。在mdm小鼠中观察到的表型差异范围远不止对肌联蛋白的影响，这清晰表明该区域的缺失会引发一系列额外的转录组变化。此前的研究多聚焦于将mdm小鼠的表型差异与肌肉功能相关联，这些研究虽阐明了该缺失所导致的下游生理效应，但仅能为可通过生理手段观测与量化的过程提供见解。本研究采用差异基因表达（DGE）技术，对比野生型与mdm小鼠的趾长伸肌（EDL）、腰大肌及比目鱼肌的转录组，以更深入地解析这些组织特异性应答反应。本研究同时开展了慢收缩型比目鱼肌与快收缩型TA肌肉组织的转录组比较研究。