Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
PLoS One. 2012;7(5):e35799. doi: 10.1371/journal.pone.0035799. Epub 2012 May 7.
To establish a genetic tool for conditional deletion or expression of gene in neurons in a temporally controlled manner, we generated a transgenic mouse (NSE-MerCreMer), which expressed a tamoxifen inducible type of Cre recombinase specifically in neurons. The tamoxifen inducible Cre recombinase (MerCreMer) is a fusion protein containing Cre recombinase with two modified estrogen receptor ligand binding domains at both ends, and is driven by the neural-specific rat neural specific enolase (NSE) promoter. A total of two transgenic lines were established, and expression of MerCreMer in neurons of the central and enteric nervous systems was confirmed. Transcript of MerCreMer was detected in several non-neural tissues such as heart, liver, and kidney in these lines. In the background of the Cre reporter mouse strain Rosa26R, Cre recombinase activity was inducible in neurons of adult NSE-MerCreMer mice treated with tamoxifen by intragastric gavage, but not in those fed with corn oil only. We conclude that NSE-MerCreMer lines will be useful for studying gene functions in neurons for the conditions that Cre-mediated recombination resulting in embryonic lethality, which precludes investigation of gene functions in neurons through later stages of development and in adult.
为了建立一种在时间上可控制的条件性删除或表达神经元中基因的遗传工具，我们生成了一种转基因小鼠（NSE-MerCreMer），其在神经元中特异性表达一种他莫昔芬诱导型 Cre 重组酶。这种他莫昔芬诱导型 Cre 重组酶（MerCreMer）是一种融合蛋白，在两端包含 Cre 重组酶和两个经过修饰的雌激素受体配体结合域，由神经特异性大鼠神经特异性烯醇化酶（NSE）启动子驱动。总共建立了两条转基因线，并证实了 MerCreMer 在中枢和肠神经系统神经元中的表达。在这些品系中，MerCreMer 的转录本在心脏、肝脏和肾脏等几种非神经组织中被检测到。在 Cre 报告小鼠品系 Rosa26R 的背景下，通过胃内灌胃给予他莫昔芬，成年 NSE-MerCreMer 小鼠的神经元中可诱导 Cre 重组酶活性，但仅用玉米油喂养则不可诱导。我们得出结论，NSE-MerCreMer 系将有助于研究神经元中基因的功能，适用于那些由于 Cre 介导的重组导致胚胎致死的情况，这些情况排除了通过发育后期和成年期来研究神经元中基因功能的可能性。
