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Duchenne muscular dystrophy (DMD) is a classical monogenic disorder, a model disease for genomic studies and a priority candidate for regenerative medicine and gene therapy. Although the genetic cause of DMD is well known, the molecular pathogenesis of disease and the response to therapy are incompletely understood. Here, we describe analyses of protein, mRNA and microRNA expression in the tibialis anterior of the mdx mouse model of DMD. Notably, 3272 proteins were quantifiable and 525 identified as differentially expressed in mdx muscle (P < 0.01). Therapeutic restoration of dystrophin by exon skipping induced widespread shifts in protein and mRNA expression towards wild-type expression levels, whereas the miRNome was largely unaffected. Comparison analyses between datasets showed that protein and mRNA ratios were only weakly correlated (r = 0.405), and identified a multitude of differentially affected cellular pathways, upstream regulators and predicted miRNA-target interactions. This study provides fundamental new insights into gene expression and regulation in dystrophic muscle.

Original publication

DOI

10.1093/hmg/ddv381

Type

Journal article

Journal

Hum Mol Genet

Publication Date

01/12/2015

Volume

24

Pages

6756 - 6768

Keywords

Animals, Disease Models, Animal, Dystrophin, Gene Expression Profiling, Genetic Therapy, Male, Mice, Mice, Inbred mdx, MicroRNAs, Muscle, Skeletal, Muscular Dystrophy, Animal, Muscular Dystrophy, Duchenne, Mutation, Proteomics, RNA, Messenger