| First Author | Martins SG | Year | 2024 |
| Journal | Life Sci Alliance | Volume | 7 |
| Issue | 12 | PubMed ID | 39379105 |
| Mgi Jnum | J:361047 | Mgi Id | MGI:7737282 |
| Doi | 10.26508/lsa.202402829 | Citation | Martins SG, et al. (2024) Laminin-alpha2 chain deficiency in skeletal muscle causes dysregulation of multiple cellular mechanisms. Life Sci Alliance 7(12) |
| abstractText | LAMA2, coding for the laminin-alpha2 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 characterized by a significant down-regulation of gene expression in muscle fibers, causing pronounced effects on cytoskeletal organization, muscle differentiation, and altered DNA repair and oxidative stress responses. Together, our findings provide unique insights into the critical importance of the laminin-alpha2 chain for muscle differentiation and muscle cell homeostasis. |
