Liu Ju, Lobe Corrinne G
Molecular and Cellular Biology Division, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
Genesis. 2007 May;45(5):259-65. doi: 10.1002/dvg.20282.
The Notch signaling pathway plays a critical role during mammalian development. To bypass embryonic lethality associated with constitutive Notch1 signaling, we created transgenic mice with a floxed beta-geo/stop signal between a cytomegalo virus promoter and the constitutively active intracellular domain of Notch1 (IC-Notch1). IC-Notch1 is activated upon introduction of Cre recombinase and it is coexpressed with an enhanced green fluorescent protein or human placental alkaline phosphatase reporter. We created three IC-Notch1 transgenic mouse lines and crossed them to a general Cre deletor mouse line, pCX-Cre. The double transgenic IC-Notch1/pCX-Cre embryos have widespread expression of IC-Notch1 and reporters and die before 10.5 days of gestation. Morphological and histological analysis of the double transgenic embryos indicated growth arrest and various developmental defects, including lack of neural tube closure, disorganized somites, and disrupted vasculature. The conditional IC-Notch1 expressing transgenic mice provide a unique tool to investigate the Notch pathway using tissue-specific Cre mice and inducible Cre systems.
Notch信号通路在哺乳动物发育过程中起着关键作用。为了绕过与组成型Notch1信号相关的胚胎致死性，我们构建了转基因小鼠，在巨细胞病毒启动子和组成型活性Notch1细胞内结构域（IC-Notch1）之间带有一个loxP侧翼的β-geo/终止信号。引入Cre重组酶后IC-Notch1被激活，并与增强型绿色荧光蛋白或人胎盘碱性磷酸酶报告基因共表达。我们构建了三个IC-Notch1转基因小鼠品系，并将它们与一种通用的Cre删除小鼠品系pCX-Cre杂交。双转基因IC-Notch1/pCX-Cre胚胎广泛表达IC-Notch1和报告基因，并在妊娠10.5天前死亡。对双转基因胚胎的形态学和组织学分析表明存在生长停滞和各种发育缺陷，包括神经管未闭合、体节紊乱和血管系统破坏。条件性表达IC-Notch1的转基因小鼠为使用组织特异性Cre小鼠和诱导性Cre系统研究Notch通路提供了一个独特的工具。
