Bortezomib Does Not Reduce Muscular Dystrophy in the dy2J/dy2J Mouse Model of Laminin α2 Chain-Deficient Muscular Dystrophy
| Autor: | Madeleine Durbeej, Zandra Körner |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
lcsh:Medicine Disease Biology Bortezomib 03 medical and health sciences Mice 0302 clinical medicine Blood plasma medicine Animals Laminin α2 Muscular dystrophy lcsh:Science Muscle Skeletal Mice Knockout Multidisciplinary lcsh:R Anatomy Muscular Dystrophy Animal medicine.disease 030104 developmental biology Treatment Outcome Proteasome inhibitor Cancer research Congenital muscular dystrophy lcsh:Q Laminin ITGA7 Proteasome Inhibitors 030217 neurology & neurosurgery medicine.drug Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 1, p e0146471 (2016) |
| ISSN: | 1932-6203 |
| Popis: | Congenital muscular dystrophy with laminin α2 chain-deficiency, also known as MDC1A, is a severe neuromuscular disorder for which there is no cure. Patients with complete laminin α2 chain-deficiency typically have an early onset disease with a more severe muscle phenotype while patients with residual laminin α2 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 α2 chain-deficiency. Still, it is possible that proteasome inhibition could be useful as a supportive therapy in patients with complete absence of laminin α2 chain. |
| Databáze: | OpenAIRE |
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