The BALB/c.mdx62 mouse exhibits a dystrophic muscle pathology and is a model of Duchenne muscular dystrophy

Swiderski, K; Chan, AS; Herold, MJ; Kueh, AJ; Chung, JD; Hardee, JP; Trieu, J; Chee, A; Naim, T; Gregorevic, P; Lynch, GS

Author(s): Swiderski, K; Chan, AS; Herold, MJ; Kueh, AJ; Chung, JD; Hardee, JP; Trieu, J; Chee, A; Naim, T; Gregorevic, P; Lynch, GS;
Details: Publication Year 2024-04-01,Volume 17,Issue #4,Page dmm050502
Journal Title: Disease Models & Mechanisms
Abstract: Duchenne muscular dystrophy (DMD) is a devastating monogenic skeletal muscle-wasting disorder. Although many pharmacological and genetic interventions have been reported in preclinical studies, few have progressed to clinical trials with meaningful benefit. Identifying therapeutic potential can be limited by availability of suitable preclinical mouse models. More rigorous testing across models with varied background strains and mutations can 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 dystrophin gene (Dmd) and the first generated in BALB/c mice. Analysis of mice at 3, 6 and 12 months of age confirmed loss of expression of the dystrophin protein isoform Dp427 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 BALB/c.mdx62 mouse is a novel model of DMD with associated variations in the immune response and muscle phenotype, compared with those of existing models. It represents an important addition to the preclinical model toolbox for developing therapeutic strategies.
Publisher: COB
Keywords: Animals; *Muscular Dystrophy, Duchenne/pathology/genetics; *Disease Models, Animal; *Mice, Inbred BALB C; *Dystrophin/metabolism/genetics; *Muscle, Skeletal/pathology/metabolism; Mice, Inbred mdx; Mice; Exons/genetics; Male; Fibrosis; Phenotype; Bone; Genetic modifier; Muscular dystrophy; Pathophysiology; Preclinical; Skeletal muscle
Research Division(s): Blood Cells And Blood Cancer
PubMed ID: 38602028
Publisher's Version: https://doi.org/10.1242/dmm.050502
Open Access at Publisher's Site: https://doi.org/0.1242/dmm.050502
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-05-08 10:06:42

Last Modified: 2024-05-08 10:44:54