Introduction of the MRL-MpJ wound-healing phenotyoe improves skeltal muscle pathology in Duchenne muscular dystrophy model mice *
MRL-MpJ mice are uniquely characterized by complete closure of ear punch wounds and have been highlighted as a mammalian model of accelerated wound-healing and tissue regeneration. However, the deficient gene in the MRL-MpJ mice has not yet been determined. In this study, we mated dystrophin-deficient Duchenne muscular dystrophy (DMD) model mdx mice (Dysmdx) with MRL-MpJ mice to generate and characterize offspring carrying Dysmdx/MRL-MpJ to investigate the effect of the MRL-MpJ wound-healing phenotype on the DMD phenotype. Single-myofiber areas (SMA) and centrally nucleated myofibers (CNF) of the quadriceps femoris muscle from the Dysmdx/MRL-MpJ mice had significantly increased at six weeks of age compared to those of the mix mice. In addition, SMA and CNF of the diaphragm in 14-week-old Dysmdx/ MRL-MpJ mice also significantly increased compared to those in the mdx mice. Moreover, the hydroxyproline content, a marker of tissue fibrosis, was significantly decreased in the 14-week-old Dysmdx/MRL-MpJ mouse diaphragm. These data suggest that introduction of the MRL/MpJ wound-healing phenotype decreases myofiber hypotrophy and accelerates myofiber regeneration by decreasing muscle fibrosis in dystrophin-deficient muscles, thereby could become a novel therapeutic option for patients with DMD. (Accepted on September 4, 2009)
