Preserved satellite cell pool in a laminin-α2-deficient model of congenital muscular dystrophy.

Abstract

Deficiency in the α2 subunit of laminin-211, encoded by LAMA2, causes congenital LAMA2-related muscular dystrophy (LAMA2 MD), characterized by severe and progressive muscle weakness. In this study, we analyzed muscle regeneration and degeneration in the gastrocnemius muscle of dy2J mice, a model of LAMA2 MD, across different ages. We found that the proportion of satellite cells (SCs) per fiber was significantly higher in the dy2J groups compared to that in the wild-type (WT) group, and that SC numbers did not decrease with disease progression. The percentages of activated SCs, and the expression of Myog and Tgfb, were also significantly elevated in affected animals compared to those in WT animals. Despite the preserved SC pool and their activation, the percentage and diameter of newly regenerated fibers progressively declined as the disease advanced. Histopathological analysis further revealed progressive fiber muscle atrophy. These results suggest that the impairment of muscle regeneration with time in the dy2J model is not due to SC depletion but rather a failure at the later stages of SC differentiation. Further investigation into these processes is essential for developing effective treatment strategies for LAMA2 MD.