Altered primary myogenesis in NFATC3(-/-) mice leads to decreased muscle size in the adult.
Signal transduction pathways involving calcineurin and its downstream effector NFAT have been implicated in regulating myogenesis. Several isoforms of NFAT exist that may differentially contribute to regulating skeletal muscle physiology. The purpose of this study was to determine the role of the NFATC3 isoform in skeletal muscle development. Adult mice lacking NFATC3 have reduced muscle mass compared to control mice. The smaller size of the muscles is not due to atrophy or blunted myofiber growth, but rather to a reduced number of myofibers. This reduction in myofiber number is not limited to a specific fiber type nor are the proportions of fiber types altered. The lower fiber number found in the adult NFATC3(-/-) mice is a consequence of impaired muscle development during embryogenesis. Immunohistochemical studies of E15 EDL muscles indicate that the total number of primary myofibers is decreased in NFATC3(-/-) embryos. At E17.5 no further decrease in primary myofiber number occurs; the size and organization of the myofibers are unaltered, and secondary myogenesis proceeds normally, suggesting a role for NFATC3 during early events in primary myogenesis. These results suggest a heretofore unknown role for the transcription factor NFAT in early skeletal muscle development.
Department of Pharmacology, Emory University School of Medicine, Atlanta, 30322, USA.
K M
KM
Kegley
J
J
Gephart
G L
GL
Warren
G K
GK
Pavlath
D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology*; D008297:Male; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018482:Muscle, Skeletal / Q000196:embryology*; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors / Q000502:physiology*
D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; C494009:Nfatc3 protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors