Genome engineering via homologous recombination in mouse embryonic stem (ES) cells: an amazingly versatile tool for the study of mammalian biology

Citation
C. Babinet et M. Cohen-tannoudji, Genome engineering via homologous recombination in mouse embryonic stem (ES) cells: an amazingly versatile tool for the study of mammalian biology, AN AC BRASI, 73(3), 2001, pp. 365-383
Citations number
64
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Multidisciplinary
Journal title
ANAIS DA ACADEMIA BRASILEIRA DE CIENCIAS
ISSN journal
0001-3765 → ACNP
Volume
73
Issue
3
Year of publication
2001
Pages
365 - 383
Database
ISI
SICI code
0001-3765(200109)73:3<365:GEVHRI>2.0.ZU;2-D
Abstract
The ability to introduce genetic modifications in the germ line of complex organisms has been a long-standing goal of those who study developmental bi ology. In this regard, the mouse, a favorite model for the study of the mam mals, is unique: indeed not only is it possible since the late seventies, t o add genes to the mouse genome like in several other complex organisms but also to perform gene replacement and modification, This has been made poss ible via two technological breakthroughs: 1) the isolation and culture of e mbryonic stem cells (ES), which have the unique ability to colonize all the tissues of an host embryo including its germ line; 2) the development of m ethods allowing homologous recombination between an incoming DNA and its co gnate chromosomal sequence (gene "targeting"). As a result, it has become p ossible to create mice bearing null mutations in any cloned gene (knock-out mice). Such a possibility has revolutionized the genetic approach of almos t all aspects of the biology of the mouse. In recent years. the scope of ge ne targeting has been widened even more, due to the refinement of the knock -out technology: other types of genetic modifications may now be created, i ncluding subtle mutations (point mutations, micro deletions or insertions, etc.) and chromosomal rearrangements such as large deletions, duplications and translocations. Finally, methods have been devised which permit the cre ation of conditional mutations, allowing the study of gene function through out the life of an animal, when gene inactivation entails embryonic lethali ty. In this paper. we present an overview of the methods and scenarios used for the programmed modification of mouse genome, and we underline their en ormous interest for the study of mammalian biology.