Female Outperformance in Voluntary Running Persists in Dystrophin-Null and Klotho-Overexpressing Mice

Background: Duchenne muscular dystrophy is a degenerative muscle disease that results from impairment of the dystrophin gene. The disease causes progressive loss in muscle mass and function. Objective: The anti-aging protein, α-klotho, has been implicated in the regulation of muscle regeneration. We previously discovered that mice harboring reduced α-klotho levels exhibited a decline in muscle strength and running endurance. Method: To investigate the ability of α-klotho to improve overall endurance in a dystrophin null murine model, we examined the voluntary wheel running performance of dystrophin-null, mdx4cv mice overexpressing an α-klotho transgene. Results: As expected, compared to wild type, both male and female dystrophic mice exhibited reduced running ability that was characterized by shorter running duration and longer periods of rest between cycles of activity. While our results did not detect an improvement in running performance with α-klotho overexpression, we identified distinct differences in the running patterns between females and males from all mouse strains analyzed (i.e., mdx4cv, mdx4cv overexpressing α-klotho, α-klotho overexpressing, α-klotho hypomorph, and wild type). For all strains, male mice displayed significantly reduced voluntary running ability compared to females. Further analysis of the mdx4cv strains demonstrated that male mice ran for shorter lengths of time and took longer breaks. However, we did not identify gender-associated differences in the actual speed at which mdx4cv mice ran. Conclusion: Our data suggest key differences in the running capabilities of female and male mice, which are of particular relevance to studies of dystrophin-null mice.