Functional analysis of muscle-specific protein, ARPP, expressed in the atrophic skeletal muscles

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Recently, we identified a novel human protein, ankyrin-repeated protein with PEST and praline-rich region (ARPP). ARPP is characterized structurally by the presence of four ankyrin-repeated domains in its central portion. The amino acid sequence of ARPP is highly homologous with that of cardiac restricted ankyrin-repeated protein (CARP; 52%). We observed high expression levels of ARPP in skeletal muscle and the heart. ARPP was selectively expressed in type 1 myofibers of skeletal muscle and, therefore, ARPP-positive myofibers were arranged in a checkerboard-like pattern. In this study, we analyzed the function of ARPP in vivo by generating ARPP knock-out (KO) mouse. Our findings are as follows;1) Compared with normal mouse, ARPP KO mouse showed decreased exercise capacity for endurance training2) ARPP expression in the skeletal muscle was found to be induced by denervation for 10 weeks.3) ARPP expression in the disuse atrophic skeletal muscle induced by tail-suspension was significantly down-regulated.4) ARPP KO mouse showed distinct expression pattern of some genes expressed specifically in the nervous system as well as skeletal muscle specific genes.5) ARPP KO mouse showed much more severe muscle injury induced by injection of cardiotoxin and delayed clearance of necrotic tissue compared with normal mouseThese findings suggest that ARPP might be concerned with the induced expression of the several proteins acting as the procetive effects in the muscle performance, muscle injury and muscle regeneration.