Cheng T C, Tseng B S, Merlie J P, Klein W H, Olson E N
Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):561-5. doi: 10.1073/pnas.92.2.561.
Myogenin, a member of the MyoD family of helix-loop-helix proteins, can induce myogenesis in a wide range of cell types. In addition to activating muscle structural genes, members of the MyoD family can autoactivate their own and cross-activate one another's expression in transfected cells. This has led to the hypothesis that autoregulatory loops among these factors provide a mechanism for amplifying and maintaining the muscle-specific gene expression program in vivo. Here, we make use of myogenin-null mice to directly test this hypothesis. To investigate whether the myogenin protein autoregulates the myogenin gene during embryogenesis, we introduced a myogenin-lacZ transgene into mice harboring a null mutation at the myogenin locus. Despite a severe deficiency of skeletal muscle in myogenin-null neonates, the myogenin-lacZ transgene was expressed normally in myogenic cells throughout embryogenesis. These results show that myogenin is not required for regulation of the myogenin gene and argue against the existence of a myogenin autoregulatory loop in the embryo.
肌细胞生成素是螺旋-环-螺旋蛋白MyoD家族的成员之一，能够在多种细胞类型中诱导肌生成。除了激活肌肉结构基因外，MyoD家族成员还能在转染细胞中自激活自身表达，并相互交叉激活彼此的表达。这引发了一种假说，即这些因子之间的自调控环为在体内放大和维持肌肉特异性基因表达程序提供了一种机制。在此，我们利用肌细胞生成素基因敲除小鼠直接检验这一假说。为了研究在胚胎发育过程中肌细胞生成素蛋白是否对肌细胞生成素基因进行自调控，我们将一个肌细胞生成素-乳糖操纵子融合基因转基因导入在肌细胞生成素基因座处有无效突变的小鼠体内。尽管肌细胞生成素基因敲除的新生小鼠严重缺乏骨骼肌，但肌细胞生成素-乳糖操纵子融合基因转基因在整个胚胎发育过程中的成肌细胞中均正常表达。这些结果表明，调控肌细胞生成素基因并不需要肌细胞生成素，这与胚胎中存在肌细胞生成素自调控环的观点相悖。
