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Linker molecules between laminins and dystroglycan ameliorate laminin-α2–deficient muscular dystrophy at all disease stages
Mutations in laminin-α2 cause a severe congenital muscular dystrophy, called MDC1A. The two main receptors that interact with laminin-α2 are dystroglycan and α7β1 integrin. We have previously shown in mouse models for MDC1A that muscle-specific overexpression of a miniaturized form of agrin (mini-ag...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2007
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064083/ https://www.ncbi.nlm.nih.gov/pubmed/17389231 http://dx.doi.org/10.1083/jcb.200611152 |
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author | Meinen, Sarina Barzaghi, Patrizia Lin, Shuo Lochmüller, Hanns Ruegg, Markus A. |
author_facet | Meinen, Sarina Barzaghi, Patrizia Lin, Shuo Lochmüller, Hanns Ruegg, Markus A. |
author_sort | Meinen, Sarina |
collection | PubMed |
description | Mutations in laminin-α2 cause a severe congenital muscular dystrophy, called MDC1A. The two main receptors that interact with laminin-α2 are dystroglycan and α7β1 integrin. We have previously shown in mouse models for MDC1A that muscle-specific overexpression of a miniaturized form of agrin (mini-agrin), which binds to dystroglycan but not to α7β1 integrin, substantially ameliorates the disease (Moll, J., P. Barzaghi, S. Lin, G. Bezakova, H. Lochmuller, E. Engvall, U. Muller, and M.A. Ruegg. 2001. Nature. 413:302–307; Bentzinger, C.F., P. Barzaghi, S. Lin, and M.A. Ruegg. 2005. Matrix Biol. 24:326–332.). Now we show that late-onset expression of mini-agrin still prolongs life span and improves overall health, although not to the same extent as early expression. Furthermore, a chimeric protein containing the dystroglycan-binding domain of perlecan has the same activities as mini-agrin in ameliorating the disease. Finally, expression of full-length agrin also slows down the disease. These experiments are conceptual proof that linking the basement membrane to dystroglycan by specifically designed molecules or by endogenous ligands, could be a means to counteract MDC1A at a progressed stage of the disease, and thus opens new possibilities for the development of treatment options for this muscular dystrophy. |
format | Text |
id | pubmed-2064083 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-20640832007-11-29 Linker molecules between laminins and dystroglycan ameliorate laminin-α2–deficient muscular dystrophy at all disease stages Meinen, Sarina Barzaghi, Patrizia Lin, Shuo Lochmüller, Hanns Ruegg, Markus A. J Cell Biol Research Articles Mutations in laminin-α2 cause a severe congenital muscular dystrophy, called MDC1A. The two main receptors that interact with laminin-α2 are dystroglycan and α7β1 integrin. We have previously shown in mouse models for MDC1A that muscle-specific overexpression of a miniaturized form of agrin (mini-agrin), which binds to dystroglycan but not to α7β1 integrin, substantially ameliorates the disease (Moll, J., P. Barzaghi, S. Lin, G. Bezakova, H. Lochmuller, E. Engvall, U. Muller, and M.A. Ruegg. 2001. Nature. 413:302–307; Bentzinger, C.F., P. Barzaghi, S. Lin, and M.A. Ruegg. 2005. Matrix Biol. 24:326–332.). Now we show that late-onset expression of mini-agrin still prolongs life span and improves overall health, although not to the same extent as early expression. Furthermore, a chimeric protein containing the dystroglycan-binding domain of perlecan has the same activities as mini-agrin in ameliorating the disease. Finally, expression of full-length agrin also slows down the disease. These experiments are conceptual proof that linking the basement membrane to dystroglycan by specifically designed molecules or by endogenous ligands, could be a means to counteract MDC1A at a progressed stage of the disease, and thus opens new possibilities for the development of treatment options for this muscular dystrophy. The Rockefeller University Press 2007-03-26 /pmc/articles/PMC2064083/ /pubmed/17389231 http://dx.doi.org/10.1083/jcb.200611152 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Meinen, Sarina Barzaghi, Patrizia Lin, Shuo Lochmüller, Hanns Ruegg, Markus A. Linker molecules between laminins and dystroglycan ameliorate laminin-α2–deficient muscular dystrophy at all disease stages |
title | Linker molecules between laminins and dystroglycan ameliorate laminin-α2–deficient muscular dystrophy at all disease stages |
title_full | Linker molecules between laminins and dystroglycan ameliorate laminin-α2–deficient muscular dystrophy at all disease stages |
title_fullStr | Linker molecules between laminins and dystroglycan ameliorate laminin-α2–deficient muscular dystrophy at all disease stages |
title_full_unstemmed | Linker molecules between laminins and dystroglycan ameliorate laminin-α2–deficient muscular dystrophy at all disease stages |
title_short | Linker molecules between laminins and dystroglycan ameliorate laminin-α2–deficient muscular dystrophy at all disease stages |
title_sort | linker molecules between laminins and dystroglycan ameliorate laminin-α2–deficient muscular dystrophy at all disease stages |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064083/ https://www.ncbi.nlm.nih.gov/pubmed/17389231 http://dx.doi.org/10.1083/jcb.200611152 |
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