Mammalian genome targeting using site-specific recombinases

被引:64
作者
García-Otín, AL
Guillou, F
机构
[1] Hosp Univ Miguel Servet, Inst Aragones Ciencias Salud, Lab Invest Mol, Zaragoza 50009, Spain
[2] Univ Tours Haras Nationnaux, CNRS, INRA, UMR 6175,Unite Physiol Reprod & Comportements, Nouzilly, France
来源
FRONTIERS IN BIOSCIENCE-LANDMARK | 2006年 / 11卷
关键词
mouse; site-specific recombinase; genetically modified mouse models; spatial and temporal gene inactivation; conditional gene targeting; review;
D O I
10.2741/1867
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nowadays, a wide array of procedures in mouse technology has been made available to researchers in order to establish valuable models for the study of gene function. The efficiency of gene transfer and gene targeting as methods for producing genetic changes in mice, in addition to continuous advances in molecular biology tools, has converted the mouse into the major experimental model for the study of mammalian physiology. In recent years, the emergence of site-specific recombinases as tools to engineer mammalian genomes has opened new avenues into the design of genetically modified mouse models. The original Cre and FLP recombinases have demonstrated their utility in developing conditional gene targeting, and now other analogous recombinases are also ready to be used, in the same way or in combined strategies, to achieve more sophisticated experimental schemes for addressing complex biological questions. The properties of sitespecific recombinases in combination with other biotechnological tools (tet on/off system, siRNA mediated gene silencing, fluorescent proteins, et al.) make them useful instruments to induce precise mutations in specific cells or tissues in a time-controlled manner. This ability can be applied in functional genomics in several ways: from conditional and inducible gene targeting to controlled expression of transgenes and recombination-mediated cassette exchange in mouse models for the study of development or disease phenotypes. This review focuses on the use of site-specific recombinases for mouse genome manipulation. A historical perspective of site-specific recombinases is considered and a number of strategies for achieving inducible or conditional genomic manipulations are contemplated in the context of current techniques for producing genetically modified mice. Finally, several model generation approaches from recent examples in the literature are revised.
引用
收藏
页码:1108 / 1136
页数:29
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