The Female mdx Mouse: An Unexpected Vascular Story

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease, caused by absence of functional dystrophin and inevitably leading to death. A variable proportion of women carriers (2.5 to 19%) can also manifest symptoms ranging from myalgia to cardiomyopathy, and pathophysiological mechanisms are still not completely understood. Our study focused on 12 month-old female mdx mice, displaying marked chronic muscle lesions, similar to the lesions observed in human DMD. Our aim was to focus on the alterations of the vascular network organisation, and functional repercussions using a combination of histology/morphometry techniques and totally non-invasive functional approach (multiparametric and functional nuclear magnetic resonance), clearly relevant for clinical diagnosis and research, combining arterial spin labeling imaging of perfusion, and 31P-spectroscopy of phosphocreatine kinetics. Collectively, our results demonstrate that the vasculature, both in its steady state organisation and dynamic behaviour after an ischemia-reperfusion stress, is altered in the 12 month-old female mdx mouse: increased density of vascular sections in histology, modification of the post-ischemic hyperemia profile, increase in mitochondrial oxidative rephosphorylation capacity, in striking opposition to what was observed in age-matched male mdx mice. We believe the apparent discordance between vascular and muscular features in the female mdx mouse make it an interesting tool to decipher further dystrophinopathy pathophysiological mechanisms.