| First Author | Gawlik KI | Year | 2014 |
| Journal | Am J Pathol | Volume | 184 |
| Issue | 3 | Pages | 740-52 |
| PubMed ID | 24393714 | Mgi Jnum | J:206359 |
| Mgi Id | MGI:5550150 | Doi | 10.1016/j.ajpath.2013.11.017 |
| Citation | Gawlik KI, et al. (2014) Loss of Dystrophin and beta-Sarcoglycan Significantly Exacerbates the Phenotype of Laminin alpha2 Chain-Deficient Animals. Am J Pathol 184(3):740-52 |
| abstractText | The adhesion molecule laminin alpha2 chain interacts with the dystrophin-glycoprotein complex, contributes to normal muscle function, and protects skeletal muscles from damage. Complete loss of the laminin alpha2 chain in mice results in a severe muscular dystrophy phenotype and death at approximately 3 weeks of age. However, it is not clear if the remaining members of the dystrophin-glycoprotein complex further protect laminin alpha2 chain-deficient skeletal muscle fibers from degeneration. Hence, we generated mice deficient in laminin alpha2 chain and dystrophin (dy(3K)/mdx) and mice devoid of laminin alpha2 chain and beta-sarcoglycan (dy(3K)/Sgcb). Severe muscular dystrophy and a lack of nourishment inevitably led to massive muscle wasting and death in double-knockout animals. The dy(3K)/Sgcb mice were generally more severely affected than dy(3K)/mdx mice. However, both double-knockout strains displayed exacerbated muscle degeneration, inflammation, fibrosis, and reduced life span (5 to 13 days) compared with single-knockout animals. However, neither extraocular nor cardiac muscle was affected in double-knockout animals. Our results suggest that, although laminin alpha2 chain, dystrophin, and beta-sarcoglycan are all part of the same adhesion complex, they have complementary, but nonredundant, roles in maintaining sarcolemmal integrity and protecting skeletal muscle fibers from damage. Moreover, the double-knockout mice could potentially serve as models in which to study extremely aggressive muscle-wasting conditions. |
