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Long-term skeletal muscle protection after gene transfer in a mouse model of LGMD-2D.

Authors: Pacak, Christina A  Walter, Glenn A  Gaidosh, Gabe  Bryant, Nathan  Lewis, Melissa A  Germain, Sean  Mah, Cathryn S  Campbell, Kevin P  Byrne, Barry J 
Citation: Pacak CA, etal., Mol Ther. 2007 Oct;15(10):1775-81. doi: 10.1038/sj.mt.6300246. Epub 2007 Jul 24.
Pubmed: (View Article at PubMed) PMID:17653106
DOI: Full-text: DOI:10.1038/sj.mt.6300246

Limb girdle muscular dystrophy (LGMD) describes a group of inherited diseases resulting from mutations in genes encoding proteins involved in maintaining skeletal muscle membrane stability. LGMD type-2D is caused by mutations in alpha-sarcoglycan (sgca). Here we describe muscle-specific gene delivery of the human sgca gene into dystrophic muscle using an adeno-associated virus 1 (AAV1) capsid and creatine kinase promoter. Delivery of this construct to adult sgca(-/-) mice resulted in localization of the sarcoglycan complex to the sarcolemma and a reduction in muscle fiber damage. Sgca expression prevented disease progression as observed in vivo by T(2)-weighted magnetic resonance imaging (MRI) and confirmed in vitro by decreased Evan's blue dye accumulation. The ability of recombinant AAV-mediated gene delivery to restore normal muscle mechanical properties in sgca(-/-) mice was verified by in vitro force mechanics on isolated extensor digitorum longus (EDL) muscles, with a decrease in passive resistance to stretch as compared with untreated controls. In summary, AAV/AAV-sgca gene transfer provides long-term muscle protection from LGMD and can be non-invasively evaluated using magnetic resonance imaging.

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RGD Object Information
RGD ID: 13605612
Created: 2018-06-11
Species: All species
Last Modified: 2018-06-11
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.