Kim J, Kim P, Hui C C
Program in Developmental Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Clin Genet. 2001 May;59(5):306-15. doi: 10.1034/j.1399-0004.2001.590503.x.
VACTERL represents a non-random association of congenital anomalies in humans of poorly known etiology and pathogenesis. From our mutant analysis of Gli genes, which encode transcription factors mediating Sonic hedgehog (Shh) signal transduction, we observed that defective Shh signaling leads to a spectrum of developmental anomalies in mice strikingly similar to those of VACTERL. In this review, we will discuss the function of the three Gli transcription factors in Shh signaling and mammalian development. We propose that VACTERL could be caused by defective Shh signaling during human embryogenesis and suggest that the Gli mutant mice can serve as useful models for studying the pathogenesis of VACTERL.
VACTERL代表了人类中病因和发病机制尚不明确的先天性异常的非随机关联。通过对Gli基因的突变分析，这些基因编码介导音猬因子（Shh）信号转导的转录因子，我们观察到Shh信号缺陷会导致小鼠出现一系列发育异常，与VACTERL的异常极为相似。在这篇综述中，我们将讨论三种Gli转录因子在Shh信号传导和哺乳动物发育中的作用。我们提出VACTERL可能是由人类胚胎发育过程中Shh信号缺陷引起的，并表明Gli突变小鼠可作为研究VACTERL发病机制的有用模型。
