Van Pelt, D., et al. Evaluating Muscle Fiber Contractility and the Transcriptome, Proteome, Metabolome, and Lipidome of the mdx/mTR Mouse Model of Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease characterized by extensive muscle weakness and eventual complete tetraplegia. The mdx mouse strain, which lacks a functional dystrophin protein, is the most frequently used small animal model in dystrophy research, but has limited pathological changes compared to patients with DMD. The mdx/mTR mouse strain, that lacks functional dystrophin and has depleted pools of muscle stem cells, is an emerging model of DMD. Previous reports have identified accelerated degeneration in mdx/mTR mice compared to mdx mice, but mdx/mTR mice have not been as extensively phenotyped. Therefore, to gain a greater understanding of the pathological changes present the mdx/mTR strain, we measured contractility of muscle fibers, and evaluated changes in the transcriptome with RNA sequencing, and in the proteome, metabolome, and lipidome using untargeted mass spectroscopy. The hindlimb muscles of four month old male wild type (WT) C57Bl/6 and mdx/mTR mice were used for analysis. We found no differences in the contractility of permeabilized muscle fibers between WT and mdx/mTR mice, but did observe divergent changes in the transcriptome and proteome, and changes in markers of skeletal muscle substrate metabolism that are informative about pathological changes in DMD.