The mdx mouse (C57BL/10ScSn-DMDmdx/J) is the oldest model of Duchenne muscular dystrophy (DMD). However, the mdx mouse has a nearly normal lifespan and mild pathology while DMD remains a severe, fatal disease. New mouse models that are more severely affected have not replaced the mdx mouse in DMD research. Here we report RNA-seq analysis of 55 wild-type and mdx mouse muscles: the hindlimb flexor digitorum brevis (FDB), extensor digitorum longus (EDL) and soleus (SOL) muscles, from 2- and 5-month-old mice. We investigate features of the mdx pathology and compare them with human DMD data. The mdx mouse muscles show enrichment of pathways related not only to inflammation and the immune response, but also to metabolic, developmental and structural pathways. The FDB shows a slower pathology development than EDL and SOL, in agreement with ex vivo experiments showing a similar age dependence of microtubule-related production of reactive oxygen species. Furthermore, the three mdx muscles show changes in over 80 genes affected in pre-symptomatic DMD patients. The mild pathology of the mdx mouse thus best mimics the early stages of DMD. This study should be helpful to those using mdx or mdx-derived mouse models to improve or develop DMD treatments.
Comparative proteomic profiling of soleus, extensor digitorum longus, flexor digitorum brevis and interosseus muscles from the mdx mouse model of Duchenne muscular dystrophy