Differentiation of muscle and the determination of ultimate tissue size.

The factors that determine ultimate muscle size have been studied using a "model" that involves two strains of mice, which had been especially bred for "largeness" (QL) and for "smallness" (QS). The difference in muscle size was not found to be due to a difference in fibre size, but due to a difference in fibre number. The muscles from the "QL" mice contained about 30% more fibres. The reason for this increased fibre number was investigated. During early development, the fusion of mononucleated presumptive myoblasts to form multinucleated myotubes took place at the same time in both "QL" and "OS" mice, as indicated by the appearance and increase in activity of ATP: creatine phosphotransferase. At this stage fibre (and cell) number and size could be determined by measuring nuclear number and protein/DNA ratio respectively. No difference in fibre (and cell) size could be found in mice at 5 days before birth, newly born, or at 20 days of age. At these ages it was found that the muscles from the "QL" mice contained a greater number of nuclei (muscle cells). The amount of RNA/nucleus was used as an index of protein synthetic rate, and no difference could be found between the large mice and the small mice. It was concluded that, in the case of the "QL" mice, the increased fibre number was not brought about by: (i) a delay in time of fusion of presumptive myoblasts; (ii) a smaller number of myoblasts fusing to form myotubes; or (iii) extensive fibre formation after fusion. Differences in fibre number, and hence muscle size, must therefore, presumably be caused by initial differences in the rate of proliferation of myoblasts before fusion.