Venuti J M, Morris J H, Vivian J L, Olson E N, Klein W H
Department of Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
J Cell Biol. 1995 Feb;128(4):563-76. doi: 10.1083/jcb.128.4.563.
Mice with a targeted mutation in the myogenic basic helix-loop-helix regulatory protein myogenin have severe muscle defects resulting in perinatal death. In this report, the effect of myogenin's absence on embryonic and fetal development is investigated. The initial events of somite differentiation occurred normally in the myogenin-mutant embryos. During primary myogenesis, muscle masses in mutant embryos developed simultaneously with control siblings, although muscle differentiation within the mutant muscle masses was delayed. More dramatic effects were observed when secondary myofibers form. During this time, very little muscle formation took place in the mutants, suggesting that the absence of myogenin affected secondary myogenesis more severely than primary myogenesis. Monitoring mutant neonates with fiber type-specific myosin isoforms indicated that different fiber types were present in the residual muscle. No evidence was found to indicate that myogenin was required for the formation of muscle in one region of the embryo and not another. The expression patterns of a MyoD-lacZ transgene in myogenin-mutant embryos demonstrated that myogenin was not essential for the activation of the MyoD gene. Together, these results indicate that late stages of embryogenesis are more dependent on myogenin than early stages, and that myogenin is not required for the initial aspects of myogenesis, including myotome formation and the appearance of myoblasts.
在生肌碱性螺旋-环-螺旋调节蛋白肌细胞生成素中发生靶向突变的小鼠存在严重的肌肉缺陷，导致围产期死亡。在本报告中，研究了肌细胞生成素缺失对胚胎和胎儿发育的影响。体节分化的初始事件在肌细胞生成素突变胚胎中正常发生。在初级肌发生过程中，突变胚胎中的肌肉块与对照同窝仔同时发育，尽管突变肌肉块内的肌肉分化延迟。在次级肌纤维形成时观察到更显著的影响。在此期间，突变体中几乎没有肌肉形成，这表明肌细胞生成素的缺失对次级肌发生的影响比对初级肌发生的影响更严重。用纤维类型特异性肌球蛋白同工型监测突变新生小鼠表明，残余肌肉中存在不同的纤维类型。没有发现证据表明肌细胞生成素在胚胎的一个区域而非另一个区域的肌肉形成中是必需的。肌细胞生成素突变胚胎中MyoD-lacZ转基因的表达模式表明，肌细胞生成素对于MyoD基因的激活不是必需的。总之，这些结果表明胚胎发育后期比早期更依赖肌细胞生成素，并且肌细胞生成素对于肌发生的初始阶段，包括肌节形成和成肌细胞的出现不是必需的。
