Gene-mediated restoration of normal myofiber elasticity in dystrophic muscles.

Details

Serval ID
serval:BIB_C5F9F028FED0
Type
Article: article from journal or magazin.
Collection
Publications
Title
Gene-mediated restoration of normal myofiber elasticity in dystrophic muscles.
Journal
Molecular Therapy
Author(s)
Puttini S., Lekka M., Dorchies O.M., Saugy D., Incitti T., Ruegg U.T., Bozzoni I., Kulik A.J., Mermod N.
ISSN
1525-0024 (Electronic)
ISSN-L
1525-0016
Publication state
Published
Issued date
2009
Volume
17
Number
1
Pages
19-25
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Dystrophin mediates a physical link between the cytoskeleton of muscle fibers and the extracellular matrix, and its absence leads to muscle degeneration and dystrophy. In this article, we show that the lack of dystrophin affects the elasticity of individual fibers within muscle tissue explants, as probed using atomic force microscopy (AFM), providing a sensitive and quantitative description of the properties of normal and dystrophic myofibers. The rescue of dystrophin expression by exon skipping or by the ectopic expression of the utrophin analogue normalized the elasticity of dystrophic muscles, and these effects were commensurate to the functional recovery of whole muscle strength. However, a more homogeneous and widespread restoration of normal elasticity was obtained by the exon-skipping approach when comparing individual myofibers. AFM may thus provide a quantification of the functional benefit of gene therapies from live tissues coupled to single-cell resolution.
Keywords
Animals, Dependovirus/genetics, Dystrophin/genetics, Elasticity, Genetic Therapy/methods, Genetic Vectors/administration & dosage, Genetic Vectors/genetics, Male, Mice, Mice, Inbred C57BL, Mice, Inbred mdx, Microscopy, Atomic Force, Muscle, Skeletal/metabolism, Muscle, Skeletal/physiopathology, Muscular Dystrophy, Animal/genetics, Muscular Dystrophy, Animal/physiopathology
Pubmed
Web of science
Open Access
Yes
Create date
23/03/2009 11:28
Last modification date
20/08/2019 16:41
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