Delayed myogenesis associated with muscle fiber hyperplasia in high-growth mice

The high-growth (hg) locus in the mouse produces a 40% increase in adult body weight and proportional hypertrophy of skeletal muscles, due to fiber hyperplasia. Using biochemical and histological criteria we tested the hypothesis that myogenesis is delayed in fetal in high-growth mice, compared with normal mice, allowing an increase in the muscle stem cell population. Significant biochemical and weight differences between lines were first apparent at embryonic day 17 (E17). At this stage, high-growth hind limbs were smaller, contained fewer nuclei, less RNA, and showed less creatine kinase (CK) activity, than controls. Histologically, high-growth muscles contained fewer, but larger, myotubes and increased extracellular matrix (at E17) compared with controls. By embryonic day 19, high-growth limbs showed increases in wet weight, CK activity, protein, RNA, and DNA compared with controls. Our results are consistent with delayed production and/or fusion of high-growth myoblasts to form secondary myotubes from embryonic day 15 to 17 and accelerated production of secondary myotubes from day 17 to 19. Delayed fusion of high-growth myoblasts may allow an increase in the muscle stem cell population, resulting in fiber hyperplasia at birth.