Myofibrillar protein synthesis in myostatin-deficient mice

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Abstract
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 (MstnΔE3/ΔE3) 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, MstnΔE3/ΔE3 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, MstnΔE3/ΔE3 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 MstnΔE3/ΔE3 mice, whereas RNA concentrations were normal, so the ratio of RNA to DNA was ∼30% greater than normal in MstnΔE3/ΔE3 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.