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1 Department of Medicine, University of Rochester, Rochester, NY, USA
2 Pathology and Laboratory Medicine in the Center for Aging and Developmental Biology, University of Rochester, Rochester, NY, USA
* To whom correspondence should be addressed. E-mail: stephen_welle{at}urmc.rochester.edu.
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 ring-2H5-L-phenylalanine. At 5-6 weeks of age, MstnE3/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 polyA RNA) concentrations in muscle. At 6 months of age, MstnE3/E3mice 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 MstnE3/E3 mice while RNA concentrations were normal, so that the ratio of RNA to DNA was ~30% greater than normal in MstnE3/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.
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