title: Gene-mediated restoration of normal myofiber elasticity in dystrophic muscles.
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.
authors.affiliation: Institute of Biotechnology, University of Lausanne, Lausanne, Switzerland.
authors.forename: Stefania
authors.initials: S
authors.lastname: Puttini
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Lekka
authors.forename: Olivier M
authors.initials: OM
authors.lastname: Dorchies
authors.forename: Damien
authors.initials: D
authors.lastname: Saugy
authors.forename: Tania
authors.initials: T
authors.lastname: Incitti
authors.forename: Urs T
authors.initials: UT
authors.lastname: Ruegg
authors.forename: Irene
authors.initials: I
authors.lastname: Bozzoni
authors.forename: Andrzej J
authors.initials: AJ
authors.lastname: Kulik
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mermod
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics; D016189:Dystrophin / Q000235:genetics*; D004548:Elasticity; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018625:Microscopy, Atomic Force; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology*; D009137:Muscular Dystrophy, Animal / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*
chemical_list: D016189:Dystrophin