Bmal1缺失抑制小鼠的肌肉再生

Objective：The physiological function of skeletal muscle is regulated by the circadian clock, but the role of the important gene Bmal1 in skeletal muscle maintenance and injury repair remains unclear.To investigate the role of Bmal1 deletion on mouse muscle regeneration. Methods:Mice with systemic knockout of Bmal1 gene were used to compare the body weight of Bmal1-/- mice and Bmal1+/- mice. Immunofluorescence staining on frozen sections of gastrocnemius from Bmal1-/- mice and wild type mice were used to compare the proportions and average cross-sectional area（CSA） of muscle fibers, and the differentiation capacity of satellite cells. A muscle injury model was constructed by injecting BaCl2 solution into tibialis anterior muscle of Bmal1-/- mice and wild type mice, and eMyHC immunofluorescence staining was performed to evaluate the regenerative capacity of injured muscles.We performed microarray analysis using satellite cells from Bmal1-/- mice and wild type mice, and differentially expressed genes that were related to myogenesis were futher validated by real time PCR. Results: Bmal1 deletion in mice resulted in reduced body weight and changed fast fibers. Loss of Bmal1 resulted in incomplete myogenic differentiation of satellite cells. Muscle regeneration impaired after damage, and newly formed fibers were inhibited in Bmal1-/- mice.The microarray data revealed increased expression of myostain（Mstn） but decreased expression of Pax7 in Bmal1-/- mice. Conclusion: Bmal1 deletion inhibits muscle regeneration by up-regulting Mstn.