Molecular, cellular and physiological investigation of myostatin propeptide-mediated muscle growth in adult mice.
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.
Matsakas
Antonios
A
School of Biological Sciences, University of Reading, Whiteknights, Reading, UK.
Foster
Keith
K
Otto
Anthony
A
Macharia
Raymond
R
Elashry
Mohamed I
MI
Feist
Simon
S
Graham
Ian
I
Foster
Helen
H
Yaworsky
Paul
P
Walsh
Frank
F
Dickson
George
G
Patel
Ketan
K
D000367:Age Factors; D000818:Animals; D049108:Cell Enlargement / Q000187:drug effects; D053145:Cell Nucleus Size / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000494:pharmacology* / Q000627:therapeutic use; D006984:Hypertrophy / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D009135:Muscular Diseases / Q000235:genetics / Q000628:therapy; D055435:Myostatin / Q000037:antagonists & inhibitors* / Q000235:genetics*; D010455:Peptides / Q000235:genetics*; D016896:Treatment Outcome
C525912:Mstn protein, mouse; D055435:Myostatin; D010455:Peptides