DELAYED MYOGENESIS ASSOCIATED WITH MUSCLE-FIBER HYPERPLASIA IN HIGH-GROWTH MICE

The high-growth (hg) locus in the mouse produces a 40% increase in adu lt body weight and proportional hypertrophy of skeletal muscles, due t o fiber hyperplasia. Using biochemical and histological criteria we te sted the hypothesis that myogenesis is delayed in fetal high-growth mi ce, compared with normal mice, allowing an increase in the muscle stem cell population. Significant biochemical and weight differences betwe en 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. Histol ogically, high-growth muscles contained fewer, but larger, myotubes an d increased extracellular matrix (at E17) compared with controls. By e mbryonic day 19, high-growth limbs showed increases in wet weight, CK activity, protein, RNA, and DNA compared with controls. Our results ar e consistent with delayed production and/or fusion of high-growth myob lasts to form secondary myotubes from embryonic day 15 to 17 and accel erated production of secondary myotubes from day 17 to 19. Delayed fus ion of high-growth myoblasts may allow an increase in the muscle stem cell population, resulting in fiber hyperplasia at birth.