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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 56 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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