Expression data from exercised-trained, myog-deleted adult mice. Mus musculus

Although skeletal muscle metabolism is a well-studied physiological process, little is known about how it is regulated at the transcriptional level. The myogenic transcription factor myogenin is required for skeletal muscle development during embryonic and fetal life, but myogenin’s role in adult skeletal muscle is unclear. We sought to determine myogenin’s function in adult muscle metabolism. A Myog conditional allele and Cre-ER transgene were used to delete Myog in adult mice. Mice were analyzed for exercise capacity by involuntary treadmill running. To assess oxidative and glycolytic metabolism, we monitored blood glucose and lactate levels and performed histochemical analysis on muscle fibers. Surprisingly, we found that Myog-deleted mice performed significantly better than controls in high- and low-intensity treadmill running. This enhanced exercise capacity was due to more efficient oxidative metabolism during low-intensity exercise and more efficient glycolytic metabolism during high-intensity exercise. Furthermore, Myog-deleted mice had an enhanced response to long-term voluntary exercise training on running wheels. We identified several candidate genes whose expression was altered in exercise-stressed muscle of mice lacking myogenin. The results suggest that myogenin plays a critical role as a high-level transcriptional regulator to control the energy balance between aerobic and anaerobic metabolism in adult skeletal muscle. We used microarrays to detail the global program of gene expression underlying enhanced exercise endurance associated with myog-deletion and long-term exercise training. Overall design: Mouse gastrocnemius muscles were selected after 6 months of myog-deletion and exercise training for RNA extraction and hybridization on Affymetrix microarrays. We chose 3 wild type and 3 myog-deleted mice that best represented the average of each larger group that was tested during our mouse exercise studies.