Irgm1 knockout indirectly inhibits regeneration after skeletal muscle injury in mice

•Irgm1−/− mice showed poor and delayed skeletal muscle injury repair.•Irgm1 knockout did not affect myoblast differentiation in vitro.•Irgm1−/− increased the levels of IFN-γ to suppress myoblast differentiation in vivo. Immunity-related GTPase family M1 protein (lRGM1) plays an important role in host resistance to infection, immune inflammation, and tumors, and it is expressed in various tissues and cells, including the central nervous system, cardiovascular system, bone marrow-derived cells, glioma, and melanoma. However, the effect of IRGM1 in the muscles has not been reported to date. In this study, Irgm1−/− mice were used to evaluate the effect of lrgm1 on regeneration after skeletal muscle injury. The tibialis anterior muscle in Irgm1−/− mice was poorly repaired after BaCl2-induced injury, whereas lrgm1 knockout itself had no significant effect on the differentiation of myoblasts. However, the microenvironment of Irgm1−/− mice with a high interferon-gamma level inhibited the differentiation of myoblasts in vivo. These results suggest that lrgm1 knockout indirectly inhibits skeletal muscle regeneration after injury, providing new insights into the biological function of IRGM1.