Impaired regenerative capacity and lower revertant fibre expansion in dystrophin-deficient mdx muscles on DBA/2 background

摘要

Duchenne muscular dystrophy, one of the most common lethal genetic disorders, is caused by mutations in the DMD gene and a lack of dystrophin protein. In most DMD patients and animal models, sporadic dystrophin-positive muscle fibres, called revertant fibres (RFs), are observed in otherwise dystrophin-negative backgrounds. RFs are thought to arise from skeletal muscle precursor cells and clonally expand with age due to the frequent regeneration of necrotic fibres. Here we examined the effects of genetic background on muscle regeneration and RF expansion by comparing dystrophin-deficient mdx mice on the C57BL/6 background (mdx-B6) with those on the DBA/2 background (mdx-DBA), which have a more severe phenotype. Interestingly, mdx-DBA muscles had significantly lower RF expansion than mdx-B6 in all age groups, including 2, 6, 12, and 18 months. The percentage of centrally nucleated fibres was also significantly lower in mdx-DBA mice compared to mdx-B6, indicating that less muscle regeneration occurs in mdx-DBA. Our study aligns with the model that RF expansion reflects the activity of precursor cells in skeletal muscles, and it serves as an index of muscle regeneration capacity.