The effects of Capn1 gene inactivation on the differential expression of genes in skeletal muscle.

Protein turnover is required for muscle growth and regeneration and several proteolytic enzymes, including the calpains, degrade myofibrillar proteins during this process. In a previous experiment, phenotypic differences were observed between μ-calpain knockout (KO) and wild type (WT) mice, including nutrient accretion and fiber type differences. These changes were particularly evident as the animals aged. Thus, we utilized 18 mice (9 KO and 9 WT) to compare transcript abundance to identify differentially expressed genes (DEGs) at 52 wk of age. A total of 55 genes were differentially expressed, including adiponectin, phosphoenolpyruvate carboxykinase 1, uncoupling protein 1, and lysine deficient protein kinase 2. These genes were analyzed for over- and underrepresented gene ontology (GO) terms. Several GO terms, including response to cytokine, response to interferon-beta, regulation of protein phosphorylation, and hydrolase activity, were identified as overrepresented. Pathways related to taurine biosynthesis, nitric oxide synthase signaling, amyloid processing, and L-cysteine degradation were also identified. Our results are consistent with previous experiments, in that identified DEGs may explain, at least in part, some of the phenotypic differences between μ-calpain KO and WT mice. Clearly muscle growth and maintenance are complex, multifaceted processes. Genes affected by the silencing of the μ-calpain gene have been identified, but the relationship between μ-calpain and these pathways requires further investigation.