Genes Whose Gain or Loss of Function Changes Type 1, 2A, 2X, or 2B Muscle Fibre Proportions in Mice-A Systematic Review

Int J Mol Sci. 2022 Oct 26;23(21):12933. doi: 10.3390/ijms232112933.


Adult skeletal muscle fibres are classified as type 1, 2A, 2X, and 2B. These classifications are based on the expression of the dominant myosin heavy chain isoform. Muscle fibre-specific gene expression and proportions of muscle fibre types change during development and in response to exercise, chronic electrical stimulation, or inactivity. To identify genes whose gain or loss-of-function alters type 1, 2A, 2X, or 2B muscle fibre proportions in mice, we conducted a systematic review of transgenic mouse studies. The systematic review was conducted in accordance with the 2009 PRISMA guidelines and the PICO framework. 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, and Vgll2) whose gain or loss-of-function significantly 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. A reanalysis of existing datasets revealed that the expression of Ppargc1a and Vgll2 increases and Mstn decreases after exercise, respectively. This suggests that these genes help to regulate the muscle fibre adaptation to exercise. Finally, there are many known DNA sequence variants of muscle fibre genes. It seems likely that such DNA sequence variants contribute to the large variation of muscle fibre type proportions in the human population.

Keywords: muscle fibre proportions; myosin heavy chain; skeletal muscle fibre.

Publication types

  • Systematic Review
  • Review

MeSH terms

  • Adult
  • Animals
  • Electric Stimulation
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Mice
  • Muscle Fibers, Skeletal* / metabolism
  • Muscle, Skeletal / metabolism
  • Myosin Heavy Chains* / genetics
  • Myosin Heavy Chains* / metabolism
  • Nuclear Receptor Co-Repressor 1 / metabolism
  • Protein Isoforms / metabolism
  • RNA-Binding Proteins / metabolism


  • Myosin Heavy Chains
  • Protein Isoforms
  • PPARGC1B protein, human
  • RNA-Binding Proteins
  • FoxJ3 protein, human
  • Forkhead Transcription Factors
  • Ncor1 protein, mouse
  • Nuclear Receptor Co-Repressor 1

Grants and funding

This research received no external funding.