Genes whose gain or loss-of-function changes type 1, 2A, 2X or 2B muscle fibre proportions in mice: A systematic literature review

Abstract

Background: Adult muscle fibres are classified as type 1, 2A, 2X, and 2B muscle fibres based on the expression of the dominant myosin heavy chain isoform. Muscle fibre-specific gene expression and muscle fibre types change during development and in response to changes in contractile activity such as exercise, chronic electrical stimulation versus inactivity or denervation. Methods: To identify genes whose gain or loss-of-function changes type 1, 2A, 2X or 2B muscle fibre proportions in mice, we conducted a systematic review following the 2020 PRISMA guidelines and the PICO framework.Results: We identified 25 “muscle fibre genes” (Akirin1, Bdkrb2, Bdnf, Camk4, Ccnd3, Cpt1a, Epas1, Esrrg, Foxj3, Foxo1, Il15, Mapk12, Mstn, Myod1, Ncor1, Nfatc1, Nol3, Ppargc1a, Ppargc1b, Sirt1, Sirt3, Thra, Thrb, Trib3, Vgll2) whose gain or loss-of-function changes type 1, 2A, 2X or 2B muscle fibre proportions in mice. The fact that 15 of the 25 muscle fibre genes are transcriptional regulators suggests that muscle fibre-specific gene expression is primarily regulated transcriptionally. Muscle fibre genes such as Ppaargc1a and Vgll2 increase or Mstn decrease their expression after exercise, respectively, suggesting that this contributes to muscle adaptation to exercise. Finally, there are many known DNA sequence variants of muscle fibre genes suggesting that this contributes to the large variation of muscle fibre percentages in humans. Conclusion: Muscle fibre genes are a set of genes that often regulate gene expression and where DNA variants are likely to change human muscle fibre distribution.