Mouse Models of Muscle Fibrosis: Mechanisms, Methods, and Applications

Skeletal muscle injuries are common and some are able to regenerate due to satellite cells, the muscle stem cell population. However, in cases of severe muscle injury, complete tears, or muscle loss via trauma, muscles can undergo fibrosis and long-term compromise of their structure and function. The development of animal models has been key to understanding the pathways involved in muscle injury, fibrosis, and repair. In this review, we discuss the animal models currently used, with a focus on those most applicable to studying muscle fibrosis after traumatic injury. We summarize the approach, findings, and limitations of the most widely used models, including volumetric muscle loss, laceration, and myotoxin injection studies, and provide a brief description of ischemia/reperfusion, crush injury, freeze injury, and dystrophy models. We summarize the histological, cellular, molecular, and functional outcome measures commonly used in the field and outline areas for translation and future work. An expansion of current studies to specifically focus on muscle fibrosis will surely elucidate novel mechanisms for reducing debilitating fibrosis and promoting regeneration.