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Molecular, cellular and physiological investigation of myostatin propeptide-mediated muscle growth in adult mice

Matsakas, A., Foster, K., Otto, A., Macharia, R., Elashry, M. I., Feist, S., Graham, I., Foster, H., Yaworsky, P., Walsh, F., Dickson, G. and Patel, K. (2009) Molecular, cellular and physiological investigation of myostatin propeptide-mediated muscle growth in adult mice. Neuromuscular Disorders, 19 (7). pp. 489-499. ISSN 0960-8966

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To link to this article DOI: 10.1016/j.nmd.2009.06.367

Abstract/Summary

Inhibition of myostatin signalling or its biological activity has recently emerged as a potential remedial approach against muscle wasting and degenerative diseases such as muscular dystrophies. In the present study we systemically administered a recombinant AAV8 vector expressing a mutated myostatin propeptide (AAV8ProMyo) to healthy mice in order to assess its impact on the histological, cellular and physiological properties of the skeletal muscle, exploiting the fact that myostatin is naturally inhibited by its own propeptide. We report that a single intravenous administration of AAV8ProMyo leads to increases in muscle mass of tibialis anterior, extensor digitorum longus and gastrocnemius muscles 8 weeks post-injection and tibialis anterior, gastrocnemius and rectus femoris muscles 17 weeks post-injection. Moreover, treatment resulted in muscle fibre hypertrophy but not hyperplasia, with IIB myofibres responding to the greatest extent following propeptide-induced myostatin inhibition. Additionally, myofibre nuclear: cytoplasmic ratio was decreased in the AAV8ProMyo treated animals. Importantly, the hypertrophic EDL muscle 8 weeks after AAV8ProMyo treatment did not show the dramatic decrease in specific force displayed by the germline myostatin null mice. (C) 2009 Elsevier B.V. All rights reserved.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Biological Sciences
Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
ID Code:9648
Uncontrolled Keywords:Myostatin, Satellite cell, Physiology, Skeletal, Muscle, Hypertrophy, Therapy, Propeptide, SKELETAL-MUSCLE, MYOBLAST PROLIFERATION, CONTRACTILE PROPERTIES, MUSCULAR-DYSTROPHY, TRANSGENIC MICE, DEFICIENT MICE, STEM-CELL, MDX, MICE, GENE, MASS

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