Muscle protein synthesis in MED myopathy

A fatal, rapidly developing progressive muscle disease of delayed onset in mice is produced by the effects of an autosomal recessive gene (MED). We recognize two stages of this disease. The earlier stage, observed between the 11th and 14th postnatal day, is characterized by structurally normal small myofibers, cessation of increase in body weight, and increasing muscular weakness, particularly of the hind limbs. The second stage is characterized by a spheromembranous degeneration of myofibers and almost complete cessation of voluntary movement. Previous studies have revealed neither anatomic abnormalities in neuromuscular junctions nor major changes in oxidative metabolism or electrolyte concentrations in striated myofibers in the early stages of the disease. In this paper we report investigations designed to determine whether the failure of growth of striated muscle in the first stage is due to a defect in muscle protein synthesis or, as has been found in muscular dystrophies, is due to an increased rate of degradation of muscle. We conclude that MED animals demonstrate a different kind of defect than that occurring in dystrophic mice. In MED mice, the failure of growth is primarily due to a diminished rate of protein synthesis.