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 inmdxmice. 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) inmdxmice 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.

Automated summary

The study showed that muscle regeneration and atrophy varied throughout the body in mouse models. Head muscles regenerated more slowly compared to limb muscles, which exhibited rapid regeneration and overgrowth. Different muscles were affected differently in muscle atrophy models caused by cancer cachexia, aging, and castration.