| First Author | Bentzinger CF | Year | 2005 |
| Journal | FASEB J | Volume | 19 |
| Issue | 8 | Pages | 934-42 |
| PubMed ID | 15923403 | Mgi Jnum | J:99653 |
| Mgi Id | MGI:3583401 | Doi | 10.1096/fj.04-3376com |
| Citation | Bentzinger CF, et al. (2005) Overexpression of mini-agrin in skeletal muscle increases muscle integrity and regenerative capacity in laminin-alpha2-deficient mice. FASEB J 19(8):934-42 |
| abstractText | Mutations in the gene encoding the alpha2 subunit of laminins cause the severe 'merosin-deficient congenital muscular dystrophy' (MDC1A). We have recently shown that overexpression of a miniaturized form of the molecule agrin (mini-agrin) counteracts the disease in dy(W)/dy(W) mice, a model for MDC1A. However, these mice express some residual truncated laminin-alpha2, suggesting that the observed amelioration might be due to mini-agrin's presenting the residual laminin-alpha2 to its receptors. Here we show that the mini-agrin counteracts the disease in dy(3K)/dy(3K) mice, which are null for laminin-alpha2. As in dy(W)/dy(W) mice, mini-agrin improves both the function and structure of muscle. We show that muscle regeneration after injury is severely impaired in dy(3K)/dy(3K) mice but is restored in the mini-agrin-expressing littermates. In summary, our results 1) show that the direct linkage of muscle basal lamina with the sarcolemma is the basis of mini-agrin-mediated amelioration and 2) provide unprecedented evidence that this linkage is important for proper regeneration of muscle fibers after injury. Our findings thus suggest that treatment with mini-agrin might be beneficial over the entire spectrum of the MDC1A disease, whose severity inversely correlates with expression levels and the size of the truncation in laminin-alpha2. |
