Conditional somatic mutagenesis in the mouse using site-specific recombinases.-猫眼课题宝

使用位点特异性重组酶对小鼠进行条件体细胞诱变。

DOI：

发表时间：

2007

期刊：

Handbook of Experimental Pharmacology

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通讯作者：

中科院分区：

文献类型：

作者：

R. Feil

在过去的十年中，位点特异性重组酶（SSRs），如Cre和Flp，已经成为小鼠基因组精确体内操作不可或缺的工具。现在，在空间和时间上控制小鼠几乎任何组织中基因敲除的发生是可行的，从而大大促进了为人类疾病和药物开发创建复杂的动物模型。本文综述了SSR技术的基本原理和现状，重点介绍了利用Cre/lox系统和配体激活的Cre重组酶进行条件体细胞诱变的策略。本课程将提供生成和分析条件小鼠突变体的实用提示，并讨论SSR技术令人兴奋的新应用，如细胞命运定位和Cre、Flp和其他生物技术工具的联合使用。它将展示通过位点特异性重组对小鼠进行遗传操作如何为人类生理学和病理生理学分析中的老问题提供新的解决方案，以及如何将其用于药物发现和开发。

In the last decade, site-specific recombinases (SSRs), such as Cre and Flp, have emerged as indispensable tools for the precise in vivo manipulation of the mouse genome. It is now feasible to control, in space and time, the onset of gene knockouts in almost any tissue of the mouse, thus greatly facilitating the creation of sophisticated animal models for human disease and drug development. This review describes the basic principles and current status of the SSR technology, with a focus on strategies for conditional somatic mutagenesis using the Cre/lox system and ligand-activated Cre recombinases. Practical hints for generating and analysing conditional mouse mutants will be given and exciting novel applications of the SSR technology will be discussed, such as cell fate mapping and the combined use of Cre, Flp and other biotechnological tools. It will be shown how genetic manipulation of the mouse by site-specific recombination can provide new solutions to old problems in the analysis of human physiology and pathophysiology and how it can be employed for drug discovery and development.