The body region specificity in murine models of muscle regeneration and atrophy.

Aim: Skeletal muscles are distributed throughout the body, presenting a variety of sizes, shapes and functions. Here, we examined whether muscle regeneration and atrophy occurred homogeneously throughout the body in mouse models.

Methods: Acute muscle regeneration was induced by a single intramuscular injection of cardiotoxin in adult mice. Chronic muscle regeneration was assessed in mdx mice. Muscle atrophy in different muscles was evaluated by cancer cachexia, ageing and castration mouse models.

Results: We found that, in the cardiotoxin-injected acute muscle injury model, head muscles slowly regenerated, while limb muscles exhibited a rapid regeneration and even overgrowth. This overgrowth was also observed in limb muscles alone (but not in head muscles) in mdx mice as chronic injury models. We described the body region-specific decline in the muscle mass in muscle atrophy models: cancer cachexia-induced, aged and castrated mice. The positional identities, including gene expression profiles and hormone sensitivity, were robustly preserved in the ectopically engrafted satellite cell-derived muscles in the castrated model.

Conclusion: Our results indicate that positional identities in muscles should be considered for the development of efficient regenerative therapies for muscle weakness, such as muscular dystrophy and age-related sarcopenia.