Nucleic Acids Research, Vol 24, Issue 4 543-548, Copyright © 1996 by Oxford University Press
Y Zhang, C Riesterer, AM Ayrall, F Sablitzky, TD Littlewood and M Reth
The site-directed recombinase Cre can be employed to delete or express
genes in cell lines or animals. Clearly, the ability to control remotely
the activity of this enzyme would be highly desirable. To this end we have
constructed expression vectors for fusion proteins consisting of the Cre
recombinase and a mutated hormone-binding domain of the murine oestrogen
receptor. The latter still binds the anti- oestrogen drug tamoxifen but no
longer 17 beta-oestradiol. We show here that in embryonic stem cells
expressing such fusion proteins, tamoxifen can efficiently induce
Cre-mediated recombination, thereby activating a stably integrated LacZ
reporter gene. In the presence of either 10 microM tamoxifen or 800 nM
4-hydroxy-tamoxifen, recombination of the LacZ gene is complete within 3-4
days. By placing a tamoxifen-binding domain on both ends of the Cre
protein, the enzymatic activity of Cre can be even more tightly controlled.
Transgenic mice expressing such an tamoxifen-inducible Cre enzyme may thus
provide a new and useful genetic tool to mutate or delete genes at specific
times during development or in adult animals.
ARTICLES
Inducible site-directed recombination in mouse embryonic stem cells
MPI fur Immunbiologie, D-79108 Freiburg, Germany.
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