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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
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