An agrin minigene rescues dystrophic symptoms in a mouse model for congenital muscular dystrophy

Joachim Moll, Patrizia Barzaghi, Shuo Lin, Gabriela Bezakova, Hanns Lochmüller, Eva Engvall, Ulrich Müller and Markus A. Ruegg ()
Additional contact information
Joachim Moll: Biozentrum, University of Basel
Patrizia Barzaghi: Biozentrum, University of Basel
Shuo Lin: Biozentrum, University of Basel
Gabriela Bezakova: Biozentrum, University of Basel
Hanns Lochmüller: Genzentrum Munich, Ludwig-Maximilians-University
Eva Engvall: The Burnham Institute
Ulrich Müller: Friedrich-Miescher Institute
Markus A. Ruegg: Biozentrum, University of Basel

Nature, 2001, vol. 413, issue 6853, 302-307

Abstract: Abstract Congenital muscular dystrophy is a heterogeneous and severe, progressive muscle-wasting disease that frequently leads to death in early childhood1,2. Most cases of congenital muscular dystrophy are caused by mutations in LAMA2, the gene encoding the α2 chain of the main laminin isoforms expressed by muscle fibres. Muscle fibre deterioration in this disease is thought to be caused by the failure to form the primary laminin scaffold, which is necessary for basement membrane structure3, and the missing interaction between muscle basement membrane and the dystrophin–glycoprotein complex (DGC)4 or the integrins5. With the aim to restore muscle function in a mouse model for this disease, we have designed a minigene of agrin, a protein known for its role in the formation of the neuromuscular junction6. Here we show that this mini-agrin—which binds to basement membrane7 and to α-dystroglycan8, a member of the DGC—amends muscle pathology by a mechanism that includes agrin-mediated stabilization of α-dystroglycan and the laminin α5 chain. Our data provides in vivo evidence that a non-homologous protein in combination with rational protein design can be used to devise therapeutic tools that may restore muscle function in human muscular dystrophies.

Date: 2001
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/35095054 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:413:y:2001:i:6853:d:10.1038_35095054

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/35095054

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().