Altered primary myogenesis in NFATC3(-/-) mice leads to decreased muscle size in the adult

Signal transduction pathways involving calcineurin and its downstream effec tor NFAT have been implicated in regulating myogenesis. Several isoforms of NFAT exist that may differentially contribute to regulating skeletal muscl e physiology. The purpose of this study was to determine the role of the NF ATC3 isoform in skeletal muscle development. Adult mice lacking NFATC3 have reduced muscle mass compared to control mice. The smaller size of the musc les is not due to atrophy or blunted myofiber growth, but rather to a reduc ed 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 studi es of E15 EDL muscles indicate that the total number of primary myofibers i s decreased in NFATC3(-/-) embryos. At E17.5 no further decrease in primary myofiber number occurs; the size and organization of the myofibers are una ltered, and secondary myogenesis proceeds normally, suggesting a role for N FATC3 during early events in primary myogenesis. These results suggest a he retofore unknown role for the transcription factor NFAT in early skeletal m uscle development. (C) 2001 Academic Press.