Weighted cart pull: A novel outcome measure for sustained motor function in mice

Sarcopenia, the pathological age-related decline in muscle mass and strength, compromises independence and quality of life in older adults. Currently, no effective treatments are available. To enhance translational research using aged mouse models, we developed and validated the weighted cart pull (WCP) as a novel assessment of sustained motor function. The WCP test involved attaching a weighted cart to the tail of a mouse as it climbed a ramp to a 'resting house'. Mass was increased incrementally until failure, defined as either five consecutive hindquarter pokes without progress or sliding backwards. In experiment 1, reliability (inter- and intra-rater) was evaluated in middle-aged mice (9 months, n = 10, 50% female). In experiment 2, young (n = 8, 50% female) and old (n = 8, 50% female) mice were tested on WCP, all-limb grip and rotarod. In experiment 3, middle-aged mice (7-9 months, n = 20, 50% female) underwent behavioural tests, in vivo electrophysiology and muscle physiology to correlate WCP with assessments of neuromuscular function. WCP showed high intra-rater repeatability [intraclass correlation coefficient = 0.611, P = 0.018, 95% confidence interval (CI) = (0.046, 0.885)]. WCP demonstrated phenotypic differences between young and old mice (Student's unpaired t-test, P < 0.0001). WCP was significantly correlated with all-limb grip [Pearson's r = 0.5820, P = 0.0071, 95% CI = (0.1878, 0.8147)], percentage decrement upon repetitive nerve stimulation at 50 Hz [Pearson's r = 0.4613, P = 0.0468, 95% CI = (0.008973, 0.7569)], twitch torque [Pearson's r = 0.6241, P = 0.0033, 95% CI = (0.2509, 0.8358)], tetanic torque [Pearson's r = 0.5100, P = 0.0216, 95% CI = (0.08718, 0.7771)] and bilateral gastrocnemius and soleus muscle mass [Pearson's r = 0.5878, P = 0.0064, 95% CI = (0.1964, 0.8177)]. The WCP provides a cost-effective, comprehensive measure of strength and sustained motor function, improving preclinical assessments.