Smith Emma, Claudinot Stéphanie, Lehal Rajwinder, Pellegrinet Luca, Barrandon Yann, Radtke Freddy
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Genesis. 2012 Sep;50(9):700-10. doi: 10.1002/dvg.22030. Epub 2012 May 3.
Signaling through the Notch1 receptor is essential for the control of numerous developmental processes during embryonic life as well as in adult tissue homeostasis and disease. Since the outcome of Notch1 signaling is highly context-dependent, and its precise physiological and pathological role in many organs is unclear, it is of great interest to localize and identify the cells that receive active Notch1 signals in vivo. Here, we report the generation and characterization of a BAC-transgenic mouse line, N1-Gal4VP16, that when crossed to a Gal4-responsive reporter mouse line allowed the identification of cells undergoing active Notch1 signaling in vivo. Analysis of embryonic and adult N1-Gal4VP16 mice demonstrated that the activation pattern of the transgene coincides with previously observed activation patterns of the endogenous Notch1 receptor. Thus, this novel reporter mouse line provides a unique tool to specifically investigate the spatial and temporal aspects of Notch1 signaling in vivo.
在胚胎期以及成体组织稳态和疾病过程中,通过Notch1受体进行的信号传导对于众多发育过程的调控至关重要。由于Notch1信号传导的结果高度依赖于背景环境,并且其在许多器官中的确切生理和病理作用尚不清楚,因此在体内定位和鉴定接收活跃Notch1信号的细胞具有极大的研究价值。在此,我们报告了一种BAC转基因小鼠品系N1-Gal4VP16的构建及其特性,该品系与Gal4反应性报告基因小鼠品系杂交后,能够在体内鉴定出经历活跃Notch1信号传导的细胞。对胚胎期和成体期N1-Gal4VP16小鼠的分析表明,转基因的激活模式与先前观察到的内源性Notch1受体的激活模式一致。因此,这种新型报告基因小鼠品系为在体内特异性研究Notch1信号传导的时空方面提供了独特的工具。