| First Author | Körner Z | Year | 2016 |
| Journal | PLoS One | Volume | 11 |
| Issue | 1 | Pages | e0146471 |
| PubMed ID | 26731667 | Mgi Jnum | J:251694 |
| Mgi Id | MGI:6092612 | Doi | 10.1371/journal.pone.0146471 |
| Citation | Korner Z, et al. (2016) Bortezomib Does Not Reduce Muscular Dystrophy in the dy2J/dy2J Mouse Model of Laminin alpha2 Chain-Deficient Muscular Dystrophy. PLoS One 11(1):e0146471 |
| abstractText | Congenital muscular dystrophy with laminin alpha2 chain-deficiency, also known as MDC1A, is a severe neuromuscular disorder for which there is no cure. Patients with complete laminin alpha2 chain-deficiency typically have an early onset disease with a more severe muscle phenotype while patients with residual laminin alpha2 chain expression usually have a milder disease course. Similar genotype-phenotype correlations can be seen in the dy3K/dy3K and dy2J/dy2J mouse models of MDC1A, respectively, with dy3K/dy3K mice presenting the more severe phenotype. Recently, we demonstrated that the proteasome inhibitor bortezomib partially improves muscle morphology and increases lifespan in dy3K/dy3K mice. Here, we explore the use of bortezomib in dy2J/dy2J animals. However, bortezomib neither improved histological hallmarks of disease nor increased muscle strength and locomotive activity in dy2J/dy2J mice. Altogether our data suggest that proteasome inhibition does not mitigate muscle dysfunction caused by partial laminin alpha2 chain-deficiency. Still, it is possible that proteasome inhibition could be useful as a supportive therapy in patients with complete absence of laminin alpha2 chain. |
