Prox1 gene transfer combined with voluntary exercise improves dystrophic muscle fragility in Mdx mice

Abstract Background Voluntary exercise can improve skeletal muscle fragility, i.e. higher susceptibility to contraction induced-injury, as shown by a greater force drop following lengthening contractions, in the dystrophic Mdx mice as compared to healthy mice with dystrophin. This beneficial effect is related to the activation of the calcineurin activation. Unfortunately, voluntary running only partly rescued fragility, so it would be interesting to combined the effects of exercise, for example, with those of others treatments activating the calcineurin pathway and promoting slow and more oxidative fibres. This is of particular interest because slow muscle fibres are apparently less affected and genetic or pharmacological treatments promoting slow and more oxidative fibres are been shown to be beneficial in the Mdx mice. Methods Here, we tested whether voluntary exercise (1 month of running in a wheel) combined with Prospero-related homeobox factor 1 gene ( Prox1) transfer would better improve functional dystrophic features in Mdx mice as compared to the voluntary exercise single approach. Prox1 is known to promote the promotion of slow contractile gene program in healthy muscle. Results We found that Prox1 transfer promoted slower molecular and functional contractile features in both voluntary exercised and sedentary Mdx mice. However, it improved fragility only in exercised Mdx mice. Moreover, Prox1 transfer reduced absolute maximal force production by causing reduction in muscle weight in both exercised and sedentary Mdx mice. Conclusion In conclusion, our results indicate that the beneficial effects of voluntary exercise and Prox1 transfer on fragility are additive in Mdx mice.