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dc.contributor.authorHagg, A
dc.contributor.authorColgan, TD
dc.contributor.authorThomson, RE
dc.contributor.authorQian, H
dc.contributor.authorLynch, GS
dc.contributor.authorGregorevic, P
dc.date.accessioned2020-06-23T13:38:09Z
dc.date.available2020-06-23T13:38:09Z
dc.date.issued2016-03-14
dc.identifierpii: srep23042
dc.identifier.citationHagg, A., Colgan, T. D., Thomson, R. E., Qian, H., Lynch, G. S. & Gregorevic, P. (2016). Using AAV vectors expressing the beta 2-adrenoceptor or associated G alpha proteins to modulate skeletal muscle mass and muscle fibre size. SCIENTIFIC REPORTS, 6 (1), https://doi.org/10.1038/srep23042.
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/11343/240784
dc.description.abstractAnabolic β2-adrenoceptor (β2-AR) agonists have been proposed as therapeutics for treating muscle wasting but concerns regarding possible off-target effects have hampered their use. We investigated whether β2-AR-mediated signalling could be modulated in skeletal muscle via gene delivery to the target tissue, thereby avoiding the risks of β2-AR agonists. In mice, intramuscular administration of a recombinant adeno-associated virus-based vector (rAAV vector) expressing the β2-AR increased muscle mass by >20% within 4 weeks. This hypertrophic response was comparable to that of 4 weeks' treatment with the β2-AR agonist formoterol, and was not ablated by mTOR inhibition. Increasing expression of inhibitory (Gαi2) and stimulatory (GαsL) G-protein subunits produced minor atrophic and hypertrophic changes in muscle mass, respectively. Furthermore, Gαi2 over-expression prevented AAV:β2-AR mediated hypertrophy. Introduction of the non-muscle Gαs isoform, GαsXL elicited hypertrophy comparable to that achieved by AAV:β2-AR. Moreover, GαsXL gene delivery was found to be capable of inducing hypertrophy in the muscles of mice lacking functional β1- and β2-ARs. These findings demonstrate that gene therapy-based interventions targeting the β2-AR pathway can promote skeletal muscle hypertrophy independent of ligand administration, and highlight novel methods for potentially modulating muscle mass in settings of disease.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.titleUsing AAV vectors expressing the beta 2-adrenoceptor or associated G alpha proteins to modulate skeletal muscle mass and muscle fibre size
dc.typeJournal Article
dc.identifier.doi10.1038/srep23042
melbourne.affiliation.departmentPhysiology
melbourne.source.titleSCIENTIFIC REPORTS
melbourne.source.volume6
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1047254
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789796
melbourne.contributor.authorLynch, Gordon
melbourne.contributor.authorCOLGAN, TIMOTHY
melbourne.contributor.authorGregorevic, Paul
melbourne.contributor.authorThomson, Rachel
melbourne.contributor.authorQian, Hongwei
dc.identifier.eissn2045-2322
pubs.acceptance.date2016-02-25
melbourne.accessrightsOpen Access


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