Strengthening Insights Into MAMDC2: Functional Characterization Of A Dystrophic Mouse Model

Illeana West

Document Type

Article

Publication Date

2025

Keywords

JMG

Abstract

MAMDC2 is a recently identified gene implicated in a novel form of autosomal dominant muscular dystrophy, yet its functional role in skeletal muscle remains unknown. This study aims to characterize the biological function of MAMDC2 by assessing muscle regenerative capacity and tissue integrity in a mouse model carrying a patient derived E668Ter truncating mutation. Baseline histological analysis revealed no signs of dystrophic pathology in the gastrocnemius muscle of wild-type (WT), heterozygous (HET) or homozygous (HOM) mice. To assess regenerative capacity under acute stress, WT mice underwent barium chloride (BaCl2) induced-muscle injury followed by time-course analysis at 3, 5, 15, and 28 days post injury (DPI) to the tibialis anterior muscle, which confirmed stereotypical stages of degeneration and regeneration. Separately, WT, HET and HOM cohorts were evaluated at 5 and 15 DPI to determine whether MAMDC2 deficiency impacts regenerative outcome. Across genotypes, all groups displayed comparable regenerative trajectories, as assessed by hematoxylin and eosin staining, centrally nucleated fiber (CNF) size, normalized TA muscle weights, and CD45+ immune cell infiltration. Muscle fiber type distribution (at homeostasis) in the soleus and extensor digitorum longus muscles, along with echocardiographic measures of cardiac function were also preserved across groups. These findings suggest that loss of MAMDC2 does not overtly impair early regeneration or homeostatic muscle composition in young adult mice. Future studies consist of applying this model on aged cohorts, assessing additional proximal muscles such as the iliopsoas, and culturing primary myoblasts to examine differentiation as a means to uncover potential delayed or tissue-specific phenotypes.

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