Gordon S. Lynch

Duchenne muscular dystrophy (DMD) is a devastating monogenic skeletal muscle wasting disorder. While many pharmacological and genetic interventions have been reported in preclinical studies, few have progressed to clinical trials with meaningful benefit. Identifying therapeutic potential may be limited by availability of suitable preclinical mouse models. More rigorous testing across models with varied background strains and mutations may identify treatments for clinical success. Here we report the generation of a DMD mouse model, with a CRISPR-induced deletion within exon 62 of the Dmd gene, and the first generated in BALB/c mice. Analysis of mice at 3, 6, and 12 months of age confirmed loss of Dp427 protein expression and resultant dystrophic pathology in limb muscles and the diaphragm, with evidence of centrally nucleated fibers, increased inflammatory markers and fibrosis, progressive decline in muscle function, and compromised trabecular bone development. The C.mdx62 mouse is a novel model of DMD with associated variations in the immune response and muscle phenotype, compared with existing models. It represents an important addition to the preclinical model toolbox for developing therapeutic strategies.