基因,蛋白,免疫 课程之蛋白组学 7.pdf

470 Engineering the mouse genome by site-specific recombination Daniel Metzger* and Robert Feil† Site-specific recombination systems are powerful tools for vivo and therefore the techniques suffer from a series of introducing predetermined modifications into eukaryotic limitations. For example, a loss-of-function mutation or genomes. Recent advances allow the manipulation of gene ‘knockout’ created by homologous recombination is chromosomal DNA in a spatially and temporally controlled present in all cells of the animal throughout pre- and post- manner in mice, offering unprecedented possibilities for natal development, thus precluding the analysis of the studying mammalian genome function and for generating gene’s function(s) in a specific cell type and at a given animal models for human diseases. time. Furthermore, these methods are not suitable for engineering complex chromosomal alterations such as Addresses large deletions, duplications, inversions and translocations. *Institut de Génétique et de Biologie Moléculaire et Cellulaire, To overcome these limitations, conventional genome mod- CNRS/INSERM/ULP, Collége de France, BP 163, 67404 Illkirch ifications have been combined with site-specific Cedex, CU de Strasbourg, France; e-mail: metzger@igbmc.u-strasbg.fr recombination systems that rely on recombinases that pro- †Institut für Pharmakologie und Toxikologie, Technische Universitä