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一种在Cdx2神经特异性增强子控制下表达Cre重组酶的新型转基因小鼠品系的特性分析。

Characterization of a novel transgenic mouse line expressing Cre recombinase under the control of the Cdx2 neural specific enhancer.

作者信息

Coutaud Baptiste, Pilon Nicolas

机构信息

Molecular Genetics of Development Laboratory, Department of Biological Sciences and BioMed Research Center, Faculty of Sciences, University of Quebec at Montreal (UQAM), Canada, H2X 3Y7.

出版信息

Genesis. 2013 Nov;51(11):777-84. doi: 10.1002/dvg.22421. Epub 2013 Aug 30.

DOI:10.1002/dvg.22421
PMID:23913642
Abstract

Several genetically modified mouse models have been generated in order to drive expression of the Cre recombinase in the neuroectoderm. However, none of them specifically targets the posterior neural plate during neurulation. To fill this gap, we have generated a new transgenic mouse line in which Cre expression is controlled by a neural specific enhancer (NSE) from the Caudal-related homeobox 2 (Cdx2) locus. Analyses of Cre activity via breeding with R26R-YFP reporter mice have indicated that the Cdx2NSE-Cre mouse line allows for recombination of LoxP sites in most cells of the posterior neural plate as soon as from the head fold stage. Detailed examination of double-transgenic embryos has revealed that this novel Cre-driver line allows targeting the entire posterior neural tube with an anterior limit in the caudal hindbrain. Of note, the Cdx2NSE regulatory sequences direct Cre expression along the whole dorso-ventral axis (including pre-migratory neural crest cells) and, accordingly, YFP fluorescence has been also observed in multiple non-cranial neural crest derivatives of double-transgenic embryos. Therefore, we believe that the Cdx2NSE-Cre mouse line represents an important novel genetic tool for the study of early events occurring in the caudal neuroectoderm during the formation of both the central and the peripheral nervous systems.

摘要

为了在神经外胚层中驱动Cre重组酶的表达,已经构建了几种转基因小鼠模型。然而,它们中没有一种在神经胚形成过程中特异性靶向神经板后部。为了填补这一空白,我们构建了一种新的转基因小鼠品系,其中Cre的表达由来自尾相关同源盒2(Cdx2)基因座的神经特异性增强子(NSE)控制。通过与R26R-YFP报告基因小鼠杂交对Cre活性进行分析表明,Cdx2NSE-Cre小鼠品系从头部折叠期开始就能使神经板后部的大多数细胞中的LoxP位点发生重组。对双转基因胚胎的详细检查显示,这种新型的Cre驱动品系能够靶向整个神经管后部,其前部界限位于后脑尾部。值得注意的是,Cdx2NSE调控序列沿整个背腹轴(包括迁移前的神经嵴细胞)指导Cre表达,因此,在双转基因胚胎的多个非颅神经嵴衍生物中也观察到了YFP荧光。因此,我们认为Cdx2NSE-Cre小鼠品系是研究中枢和外周神经系统形成过程中尾侧神经外胚层发生的早期事件的一种重要的新型遗传工具。

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