Establishing a Functional Model of Mouse Muscle Injury and Recovery

Abstract

PURPOSE: To establish an in vivo mouse model of muscle injury and recovery. METHODS: Sixteen genetically identical female mice were randomized to two 8-mouse injury cohorts (either Phosphate Buffered Saline (PBS) (control) or cardiotoxin (injured)). Injections were performed unilaterally to the right tibialis anterior. One protocol (nocturnal wheel running) was evaluated longitudinally throughout the 17 day study period, while the remaining 5 protocols (dynamic weight bearing, treadmill gait analysis, Rota-Rod performance, open field testing, and grip strength) were evaluated as one-time assays over post-injury days 5-6. All experiments were conducted at Jackson Laboratory, Bar Harbor, Maine. RESULTS: Of the six protocols examined, only the Rota-Rod assay demonstrated a statistically significant difference between injured and control mice (p<0.0018). The Rota-Rod is a rotating rod that increases velocity until the mouse is no longer able to stay on and falls to a soft surface for a maximum trial duration of 300 seconds. The mean latency (seconds until falling) was 298 seconds for control mice and 186 seconds for cardiotoxin-injured mice, with a significant difference of 111 seconds (95% CI 17.0-205.5). There was no significant difference in the two groups in terms of wheel running, weight bearing, gait, open field, or grip strength. CONCLUSION: The Rota-Rod consistently and significantly delineated between cardiotoxin-injured mice and placebo mice at day 5 post-injury. It is likely that even greater statistical significance would result from Rota-Rod trials lasting greater than 300 seconds. It is unknown how Rota-Rod would perform at other time points. Unilateral cardiotoxin injection to the tibialis anterior and subsequent Rota-Rod trial provides a low cost easy to perform in vivo murine model of muscle injury functional assessment within which novel therapies can be assessed.