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

Authors: Oliver, William; Keel, Brittney; Lindholm-Perry, Amanda; HORODYSKA, JUSTYNA - Teagasc (AGRICULTURE AND FOOD DEVELOPMENT AUTHORITY); Foote, Andrew

Submitted to: Gene
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/13/2018
Publication Date: 8/20/2018
Citation: Oliver, W.T., Keel, B.N., Lindholm-Perry, A.K., Horodyska, J., Foote, A.P. 2018. The effects of Capn1 gene inactivation on the differential expression of genes in skeletal muscle. Gene. 668:54-58. https://doi.org/10.1016/j.gene.2018.05.040.
DOI: https://doi.org/10.1016/j.gene.2018.05.040

Interpretive Summary: Protein turnover is unique due to the structure of muscle fibers. Turnover must be accomplished through degradation of proteins by a protease system on the surface of the muscle fiber without disrupting this structure. The µ-calpain is part of this protease system. Previous research from the U.S. Meat Animal Research Center (USMARC) has shown differences in protein and fat metabolism in mice that do not express µ-calpain. Understanding the role of µ-calpain in these processes will allow for opportunities to target the calpain system to promote the growth and/or restoration of skeletal muscle mass. Research conducted at the USMARC described the expression of genes in skeletal muscle in mice that do not have µ-calpain compared to normal mice that do. Fifty-five genes were shown to be different between the groups and several of them help to explain, at least in part, some of the differences caused by a lack of µ-calpain. These include a higher abundance of the genes Cdo1 and Prkar2b and a lower abundance of the genes Nos1 and Wnk2. Thus, genes have been identified as potential targets to utilize the calpain system to promote muscle growth.

Technical Abstract: 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.