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在纯C57BL/6遗传背景上进行条件性基因靶向。

Conditional gene targeting on the pure C57BL/6 genetic background.

作者信息

Mishina Masayoshi, Sakimura Kenji

机构信息

Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan.

出版信息

Neurosci Res. 2007 Jun;58(2):105-12. doi: 10.1016/j.neures.2007.01.004. Epub 2007 Jan 18.

Abstract

Brain functions are the products of dynamic interactions between multiple genes and environments. Accordingly, there are large differences among mouse strains at the behavioral and neurobiological levels. Therefore, it is crucial to manipulate genes on the same and homogenous genetic background and then to analyze and compare the phenotypes of various genetically modified mice. Furthermore, a conditional gene targeting to restrict the gene knockout to specific cells and time is a powerful tool to investigate the molecular basis of higher brain functions such as learning and memory. We have developed a system employing Cre-progesterone receptor fusion recombinase for temporal regulation of gene targeting and Flp/frt recombination system for elimination of marker genes. Importantly, both the recombinase lines and target mice have been produced with embryonic stem cells derived from the C57BL/6 strain suitable for brain function analysis. Thus, we have established an inducible and neuron-specific gene targeting system on the pure C57BL/6 genetic background.

摘要

脑功能是多个基因与环境之间动态相互作用的产物。因此,不同小鼠品系在行为和神经生物学水平上存在很大差异。所以,在相同且同质的遗传背景下操纵基因,然后分析和比较各种基因修饰小鼠的表型至关重要。此外,一种能将基因敲除限制在特定细胞和特定时间的条件性基因打靶技术,是研究学习和记忆等高级脑功能分子基础的有力工具。我们开发了一种系统,该系统采用Cre-孕酮受体融合重组酶进行基因打靶的时间调控,以及Flp/frt重组系统来消除标记基因。重要的是,重组酶品系和靶小鼠均由源自适合脑功能分析的C57BL/6品系的胚胎干细胞产生。因此,我们在纯C57BL/6遗传背景上建立了一种诱导性且神经元特异性的基因打靶系统。

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