MUSTN1 Interaction With SMPX Regulates Muscle Development and Regeneration

ABSTRACT Pigs are important agricultural animals whose growth rate and meat production performance are related to muscle development. Musculoskeletal embryonic nuclear protein 1 (MUSTN1) participates in various biological processes, including myogenesis and growth in animals, but the physiological functions and mechanisms of porcine MUSTN1 on muscle development are unclear; thus, we aimed to elucidate them. We found that MUSTN1 was highly expressed in the muscles of fast‐growing pigs. Functionally, MUSTN1 promoted myoblast proliferation and differentiation. MUSTN1 knockout mice exhibited reduced muscle mass and fibre cross‐sectional area, decreased exercise endurance, and delayed muscle regeneration. Small muscle protein X‐linked (SMPX) was identified as an interacting protein of MUSTN1, and its promotion of myogenic differentiation depended on MUSTN1. Furthermore, MUSTN1 stabilised SMPX and maintained myofiber morphology. This study suggests that MUSTN1 is a critical regulator in the control of muscle development and regeneration and is a potential target for animal genetic improvement and the treatment of human muscle disease.