Tie2-Cre transgenic mice:: A new model for endothelial cell-lineage analysis in vivo

Tie2-Cre transgenic mice:: A new model for endothelial cell-lineage analysis in vivo
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DOI:
10.1006/dbio.2000.0106
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发表时间:
2001-02-15
影响因子:
2.7
通讯作者:
Yanagisawa, M
Yanagisawa, M
中科院分区:
生物学3区
文献类型:
--
作者:
Kisanuki, YY;Hammer, RE;Yanagisawa, M

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心内膜细胞被认为至少在一定程度上参与了心内膜垫间充质的形成。在此,我们构建了Tie2 - Cre转基因小鼠,其中Cre重组酶的表达由一个内皮特异性启动子/增强子驱动。为了分析表达Cre的细胞的谱系,我们使用了CAG - CAT - Z转基因小鼠,其中lacZ的表达只有在Cre介导的重组之后才被激活。我们在Tie2 - Cre;CAG - CAT - Z双转基因小鼠中检测到Cre转基因的泛内皮表达。这种表达模式几乎与Tie2 - lacZ转基因小鼠相同。然而,有趣的是,我们在Tie2 - Cre;CAG - CAT - Z双转基因小鼠的房室管间充质细胞中观察到强烈且均匀的lacZ表达。我们还在部分近端心脏流出道的间充质细胞中检测到lacZ表达,但在远端流出道和鳃弓动脉的间充质细胞中未检测到。Tie2 - Cre;CAG - CAT - Z胚胎中的lacZ染色与房室管和流出道区域的心内膜 - 间充质转化是一致的。我们的观察结果与先前报道的来自Cx43 - lacZ、Wnt1 - Cre;R26R和Pax3 - Cre;R26R转基因小鼠的结果一致,在这些小鼠中,心脏流出道中的lacZ表达表明部分来源于心脏神经嵴。Tie2 - Cre转基因小鼠是一种用于分析内皮细胞谱系和内皮细胞特异性基因靶向的新型遗传工具。(C)2001年学术出版社
Endocardial cells are thought to contribute at least in part to the formation of the endocardial cushion mesenchyme. Here, we created Tie2-Cre transgenic mice, in which expression of Cre recombinase is driven by an endothelial-specific promoter/enhancer. To analyze the lineage of Cre expressing cells, we used CAG-CAT-Z transgenic mice, in which expression of lacZ is activated only after Cre-mediated recombination. We detected pan-endothelial expression of the Cre transgene in Tie2-Cre;CAG-CAT-Z double-transgenic mice. This expression pattern is almost identical to Tie2-lacZ transgenic mice. However, interestingly, we observed strong and uniform lacZ expression in mesenchymal cells of the atrioventricular canal of Tie2-Cre;CAG-CAT-Z double-transgenic mice. We also detected lacZ expression in the mesenchymal cells in part of the proximal cardiac outflow tract, but not in the mesenchymal cells of the distal outflow tract and branchial arch arteries. LacZ staining in Tie2-Cre;CAG-CAT-Z embryos is consistent with endocardial-mesenchymal transformation in the atrioventricular canal and outflow tract regions. Our observations are consistent with previously reported results from Cx43-lacZ, Wnt1-Cre;R26R, and Pax3-Cre;R26R transgenic mice, in which lacZ expression in the cardiac outflow tract identified contributions in part from the cardiac neural crest. Tie2-Cre transgenic mice are a new genetic tool for the analyses of endothelial cell-lineage and endothelial cell-specific gene targeting. (C) 2001 Academic Press.