Knockout Of Myostatin Gene Suppress Three Tricarboxylic Acid Cycle And Oxidative Phosphorylation In The Skeletal Muscle Of Mice

Myostatin(MSTN)belongs to the transforming growth factor-beta(TGF-?)super-family,which participate extensively in the regulation of body development.Mutations of MSTN are known to cause a double muscle mass phenotype in several mammals,including cattle,sheep,dogs,mice and humans.MSTN is a negative regulator of myogenesis,which take part in muscle development and differentiation.The metabolism of myoblast also affected by MSTN.To study the functions of MSTN in metabolism of skeletal muscle,MSTN knockout mice were generated by CRISPR/Cas9 system with a deletion at the third exon.The MSTN-/-mice were used to evaluate the effect of MSTN on skeletal muscle basal metabolic activity and mitochondrial function.The results were as follows:1)the MSTN gene expression level decreased in different organs;2)the body weight of MSTN-/-mice increased significantly when compared to control mice;3)the MSTN-/-mice had a lower body temperature and basal metabolic rate;4)MSTN knockout significantly affected the myofibrillar mitochondrial function in skeletal muscle,which enhanced the beta oxidation of fatty acids and suppressed the tricarboxylic acid cycle and oxidative phosphorylation;5)The gene expression of mitochondrial synthesis related genes,TFAM,Nrfl and Clpp,and mitochondrial antioxidant related genes,SOD and GSH,were also significantly,were significantly up-regulated.The results indicated that,knockout of MSTN significantly altered the basic metabolism of mice,and suppressed the tricarboxylic acid cycle and oxidative phosphorylation in the mitochondria of skeletal muscle cells.