Titre :
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Non invasive demonstration of muscle recovery after AAV transfer of therapeutic DNA in mdx and alpha-sarcoglycan-null mutant mice using murine secreted alkaline phosphatase as reporter (abstract : congrès international de Myologie, 2005)
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contenu dans :
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Auteurs :
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Congrès international de myologie 2005 (International Congress of Myology 2005; 9-13 mai 2005; Nantes, France) ;
Bartoli M ;
Poupiot J ;
Goyenvalle A ;
Garcia L ;
Danos O ;
Richard I
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Type de document :
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Article
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Année de publication :
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2005
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Pages :
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p. 272
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Langues:
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Anglais
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Mots-clés :
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alpha-sarcoglycane
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colloque
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complexe dystrophine
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dégenérescence de la fibre musculaire
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dystrophie musculaire de Duchenne
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gène DMD
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mutation génétique
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myofibrille
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phosphatase alcaline
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régénération musculaire
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saut d'exon
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souris
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souris mdx
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thérapie génique
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vecteur adénoassocié
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Résumé :
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Communication n° 222 Muscular dystrophies are a genetically and phenotypically heterogeneous group of degenerative muscle diseases. A subset of them are due to genetic deficiencies in proteins participating in the dystrophin-associated complex at the membrane of the myofibers. In this report, we utilized recombinant AAV containing a U7 cassette carrying antisense sequence aimed at inducing exon skipping of the dystrophin gene or containing the alpha-sarcoglycan gene to alleviate the dystrophic phenotype of the mdx and Sgca-null mice, respectively. As these diseases are characterized by cycle of degeneration regeneration, we postulated that a reporter gene co-administrated at the time of the treatment would allow to follow the extend of muscle reparation. We observed that the murine secreted alkaline phosphatase (muSeAP) level was very much less in these animal models than in normal mice. Upon treatment of the dystrophic muscle by gene transfer experiment, the level of muSeAP is restored and correlated with the expression of the therapeutic transgene and with the level of muscle improvement. The system described in this poster provides a simple and non-invasive procedure to monitor the outcome of a therapeutic strategy involving cell survival.
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