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This Article Full Text Full Text (PDF) All Versions of this Article: 290/3/E409    most recent 00433.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Welle, S. Articles by Pinkert, C. A. Search for Related Content PubMed PubMed Citation Articles by Welle, S. Articles by Pinkert, C. A.

Myofibrillar protein synthesis in myostatin-deficient mice

Departments of ¹Medicine and ²Pathology and Laboratory Medicine in the Center for Aging and Developmental Biology, University of Rochester, Rochester, New York

Submitted 9 September 2005 ; accepted in final form 3 October 2005

Either increased protein synthesis or prolonged protein half-life is necessary to support the excessive muscle growth and maintenance of enlarged muscles in myostatin-deficient mice. This issue was addressed by determining in vivo rates of myofibrillar protein synthesis in mice with constitutive myostatin deficiency (Mstn^E3/E3) or normal myostatin expression (Mstn^+/+) by measuring tracer incorporation after a systemic flooding dose of L-[ring-²H₅]phenylalanine. At 5–6 wk of age, Mstn^E3/E3 mice had increased muscle mass (40%), fractional rates of myofibrillar synthesis (14%), and protein synthesis per whole muscle (60%) relative to Mstn^+/+ mice. With maturation, fractional rates of synthesis declined >50% in parallel with decreased DNA and RNA [total, 28S rRNA, and poly(A) RNA] concentrations in muscle. At 6 mo of age, Mstn^E3/E3 mice had even greater increases in muscle mass (90%) and myofibrillar synthesis per muscle (85%) relative to Mstn^+/+ mice, but the fractional rate of synthesis was normal. Estimated myofibrillar protein half-life was not affected by myostatin deficiency. Muscle DNA concentrations were reduced in both young and mature Mstn^E3/E3 mice, whereas RNA concentrations were normal, so the ratio of RNA to DNA was 30% greater than normal in Mstn^E3/E3 mice. Thus the increased protein synthesis and RNA content per muscle in myostatin-deficient mice cannot be explained entirely by an increased number of myonuclei.

muscle growth; ribonucleic acid; deoxyribonucleic acid; ubiquitin; cathepsin B

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