Kegley K M, Gephart J, Warren G L, Pavlath G K
Department of Pharmacology, Emory University School of Medicine, Atlanta, 30322, USA.
Dev Biol. 2001 Apr 1;232(1):115-26. doi: 10.1006/dbio.2001.0179.
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.
涉及钙调神经磷酸酶及其下游效应分子NFAT的信号转导通路与肌生成调节有关。存在几种NFAT亚型，它们可能对骨骼肌生理调节有不同作用。本研究的目的是确定NFATC3亚型在骨骼肌发育中的作用。与对照小鼠相比，缺乏NFATC3的成年小鼠肌肉质量降低。肌肉较小并非由于萎缩或肌纤维生长受阻，而是由于肌纤维数量减少。肌纤维数量的减少并不局限于特定的纤维类型，纤维类型的比例也未改变。成年NFATC3(-/-)小鼠中较低的纤维数量是胚胎发育过程中肌肉发育受损的结果。对E15期趾长伸肌（EDL）的免疫组织化学研究表明，NFATC3(-/-)胚胎中初级肌纤维的总数减少。在E17.5期，初级肌纤维数量不再进一步减少；肌纤维的大小和组织结构未改变，次级肌生成正常进行，这表明NFATC3在初级肌生成的早期事件中发挥作用。这些结果表明转录因子NFAT在早期骨骼肌发育中具有迄今未知的作用。
