Elucidation and application of skeletal muscle regulation mechanisms using mouse space experiments

Abstract

The effects of the microgravity environment in space on skeletal muscles have been analyzed by various space experiments, but it has been technically difficult to scientifically analyze the threshold of gravity effects. To elucidate this problem, a small animal breeding apparatus with a centrifuge that can generate artificial gravity in the space environment was installed on the International Space Station. In collaboration with the Japan Aerospace Exploration Agency (JAXA), we used this apparatus to raise mice under several gravity environments and analyzed the effects of gravity on skeletal muscles. The results showed that, as expected, microgravity-induced muscle atrophy and increase of fast twice muscle fibers were completely suppressed in artificial 1g (earth gravity). On the other hand, 1/6 g (lunar gravity) suppressed muscle atrophy but not increase of fast twitch muscle fibers. These results suggest that muscle atrophy and myofiber change are independently regulated. To analyze the molecular mechanisms, gene expression analysis was performed to analyze the genes that fluctuate in response to the gravitational environment. From this analysis, we identified a previously uncharacterized Large Maf transcription factor that induces fast twitch muscle fibers. Overexpression of the Large Maf transcription factor in skeletal muscle induced fast-twitch type IIb fibers. Deletion of the Large Maf transcription factor in skeletal muscle resulted in little formation of type IIb fibers. Furthermore, this mechanism is conserved across animal species. These results indicate that the Large Maf transcription factor is a major transcription factor that induces Type IIb fibers across animal species.