edoc

Overexpression of mini-agrin in skeletal muscle increases muscle integrity and regenerative capacity in laminin-alpha2-deficient mice

Bentzinger, C. F. and Barzaghi, P. and Lin, S. and Ruegg, M. A.. (2005) Overexpression of mini-agrin in skeletal muscle increases muscle integrity and regenerative capacity in laminin-alpha2-deficient mice. FASEB Journal, 19 (8). pp. 934-942.

[img] PDF - Published Version
Restricted to Repository staff only

517Kb

Official URL: http://edoc.unibas.ch/dok/A5258390

Downloads: Statistics Overview

Abstract

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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Neurobiology > Pharmacology/Neurobiology (Rüegg)
UniBasel Contributors:Rüegg, Markus A.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Federation of American Society of Experimental Biology
ISSN:0892-6638
e-ISSN:1530-6860
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
edoc DOI:
Last Modified:16 Apr 2019 12:02
Deposited On:22 Mar 2012 13:29

Repository Staff Only: item control page