Myofibrillar protein synthesis in myostatin-deficient mice

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(Delta E3/Delta E3)) or normal myostatin expression ( Mstn(+/+)) by measuring tracer incorporation after a systemic flooding dose of L-[ ring-H-2(5)] phenylalanine. At 5 - 6 wk of age, Mstn(Delta E3/Delta 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(Delta E3/Delta 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(Delta E3/Delta E3) mice, whereas RNA concentrations were normal, so the ratio of RNA to DNA was similar to 30% greater than normal in Mstn(Delta E3/Delta 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.