Relative quantification of progressive changes in healthy and dysferlin‐deficient mouse skeletal muscle proteomes

Introduction/AimsIndividuals with dysferlinopathies, a group of genetic muscle diseases, experience delay in the onset of muscle weakness. The cause of this delay and subsequent muscle wasting are unknown, and there are currently no clinical interventions to limit or prevent muscle weakness. To better understand molecular drivers of dysferlinopathies, age‐dependent changes in the proteomic profile of skeletal muscle (SM) in wild‐type (WT) and dysferlin‐deficient mice were identified.MethodsQuadriceps were isolated from 6‐, 18‐, 42‐, and 77‐wk‐old C57BL/6 (WT, Dysf+/+) and BLAJ (Dysf−/−) mice (n = 3, 2 male/1 female or 1 male/2 female, 24 total). Whole‐muscle proteomes were characterized using liquid chromatography‐mass spectrometry with relative quantification using TMT10plex isobaric labeling. Principle component analysis was utilized to detect age‐dependent proteomic differences over the lifespan of, and between, WT and dysferlin‐deficient SM. The biological relevance of proteins with significant variation was established using Ingenuity Pathway Analysis.ResultsOver 3200 proteins were identified between 6‐, 18‐, 42‐, and 77‐wk‐old mice. In total, 46 proteins varied in aging WT SM (p