Transcription profiling by array of mdx mouse gastrocnemius muscle

Despite over 3,000 articles published on dystrophin in the last 15 years, the reasons underlying the progression of the human disease, differential muscle involvement, and disparate phenotypes in different species are not understood. The present experiment employed a screen of 12,488 mRNAs in 16-wk-old mouse mdx muscle at a time when the skeletal muscle is avoiding severe dystrophic pathophysiology, despite the absence of a functional dystrophin protein. A number of transcripts whose levels differed between the mdx and human Duchenne muscular dystrophy were noted. A fourfold decrease in myostatin mRNA in the mdx muscle was noted. Differential upregulation of actin-related protein 2/3 (subunit 4), beta-thymosin, calponin, mast cell chymase, and guanidinoacetate methyltransferase mRNA in the more benign mdx was also observed. Transcripts for oxidative and glycolytic enzymes in mdx muscle were not downregulated. These discrepancies could provide candidates for salvage pathways that maintain skeletal muscle integrity in the absence of a functional dystrophin protein in mdx skeletal muscle.尽管近15年间已有超过3000篇关于肌营养不良蛋白（dystrophin）的研究论文发表，但人类肌病进展、肌肉差异性受累以及不同物种间表型差异的潜在分子机制仍未阐明。本研究对16周龄mdx小鼠的骨骼肌进行了12488种mRNA的转录组筛选——此时该模型小鼠的骨骼肌虽缺乏功能性肌营养不良蛋白，却可避免严重的营养不良性病理生理改变。研究鉴定出一批在mdx小鼠与人类杜氏肌营养不良症（Duchenne muscular dystrophy）中表达水平存在显著差异的转录本：实验观察到mdx小鼠肌肉内肌抑素（myostatin）的mRNA水平下降了四倍；此外，在病情更为温和的mdx模型中，还观测到肌动蛋白相关蛋白2/3（亚基4）、β-胸腺素（beta-thymosin）、钙调蛋白（calponin）、肥大细胞糜蛋白酶（mast cell chymase）以及胍乙酸甲基转移酶（guanidinoacetate methyltransferase）的mRNA发生差异性上调。mdx小鼠肌肉内氧化酶与糖酵解酶的转录本并未出现表达下调。上述转录表达差异可为阐明mdx小鼠骨骼肌在缺乏功能性肌营养不良蛋白的情况下维持肌肉结构完整性的挽救通路提供潜在候选靶点。