Conditional gene targeting on the pure C57BL/6 genetic background

Conditional gene targeting on the pure C57BL/6 genetic background
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DOI:
10.1016/j.neures.2007.01.004
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发表时间:
2007-06-01
影响因子:
2.9
通讯作者:
Sakimura, Kenji
Sakimura, Kenji
中科院分区:
医学4区
文献类型:
--
作者:
Mishina, Masayoshi;Sakimura, Kenji

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大脑功能是多个基因和环境之间动态相互作用的产物。因此,不同品系的小鼠在行为和神经生物学水平上存在很大差异。因此,在相同和同质的遗传背景下操纵基因,然后分析和比较各种转基因小鼠的表型是至关重要的。此外,有条件的基因打靶将基因敲除限制在特定的细胞和时间,是研究大脑高级功能(如学习和记忆)的分子基础的有力工具。我们已经开发了一个系统,采用Cre-孕酮受体融合重组酶的时间调节基因打靶和Flp/frt重组系统消除标记基因。重要的是,重组酶系和靶小鼠都是用源自适合于脑功能分析的C57 BL/6品系的胚胎干细胞产生的。因此,我们建立了一个可诱导的和神经元特异性的基因打靶系统的纯C57 BL/6的遗传背景。(c)2007 Elsevier爱尔兰有限公司和日本神经科学学会。All rights reserved.
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. (c) 2007 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.