Laminin-α2 chain deficiency in skeletal muscle causes dysregulation of multiple cellular mechanisms.

ABSTRACT: LAMA2, coding for the laminin-α2 chain, is a crucial ECM component, particularly abundant in skeletal muscle. Mutations in LAMA2 trigger the often-lethal LAMA2-congenital muscular dystrophy (LAMA2-CMD). Various phenotypes have been linked to LAMA2-CMD; nevertheless, the precise mechanisms that malfunction during disease onset in utero remain unknown. We generated Lama2-deficient C2C12 cells and found that Lama2-deficient myoblasts display proliferation, differentiation, and fusion defects, DNA damage, oxidative stress, and mitochondrial dysfunction. Moreover, fetal myoblasts isolated from the dy ^W mouse model of LAMA2-CMD display impaired differentiation and fusion in vitro. We also showed that disease onset during fetal development is c

SUBMITTER: Martins SG 

PROVIDER: S-EPMC11463332 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature