Molecular Human Reproduction, Vol 4, 929-938, Copyright © 1998 by Oxford University Press
M Cohen-Tannoudji and C Babinet
The emergence of gene inactivation by homologous recombination methodology
in embryonic stem cells has revolutionized the field of mouse genetics.
Indeed, the availability of a rapidly growing number of mouse null mutants
has represented an invaluable source of knowledge on mammalian development,
cellular biology and physiology and has provided many models for human
inherited diseases. In recent years, improvements of the original
'knock-out' strategy, as well as the exploitation of exogenous enzymatic
systems that are active in the recombination process, have considerably
extended the range of genetic manipulations that can be produced. For
example, it is now possible to create a mouse bearing a targeted point
mutation as the unique change in its entire genome therefore allowing very
fine dissection of gene function in vivo. Chromosome alterations such as
large deletions, inversions or translocations can also be designed and will
facilitate the global functional analysis of the mouse genome. This will
extend the possibilities of creating models of human pathologies that
frequently originate from various chromosomal disorders. Finally, the
advent of methods allowing conditional gene targeting will open the way for
the analysis of the consequence of a particular mutation in a defined organ
and at a specific time during the life of a mouse.
REVIEW, TUTORIAL
Beyond 'knock-out' mice: new perspectives for the programmed modification of the mammalian genome
Unite de Biologie du Developpement, CNRS URA 1960, Institut Pasteur, Paris, France.
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