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Abstract
The ability to generate specific genetic modifications in mice provides a powerful
approach to assess gene function. When genetic modifications have been generated in
the germ line, however, the resulting phenotype often only reflects the first time
a gene has an influence on - or is necessary for - a particular biological process.
Therefore, systems allowing conditional genetic modification have been developed (for
a review, see [1]); for example, inducible forms of the Cre recombinase from P1 phage
have been generated that can catalyse intramolecular recombination between target
recognition sequences (loxP sites) in response to ligand [2] [3] [4] [5]. Here, we
assessed whether a tamoxifen-inducible form of Cre recombinase (Cre-ERTM) could be
used to modify gene activity in the mouse embryo in utero. Using the enhancer of the
Wnt1 gene to restrict the expression of Cre-ERTM to the embryonic neural tube, we
found that a single injection of tamoxifen into pregnant mice induced Cre-mediated
recombination within the embryonic central nervous system, thereby activating expression
of a reporter gene. Induction was ligand dependent, rapid and efficient. The results
demonstrate that tamoxifen-inducible recombination can be used to effectively modify
gene function in the mouse embryo.