A multifunctional reporter mouse line for Cre- and FLP-dependent lineage analysis.

The Cre/lox and FLP/FRT recombination systems have been used extensively for both conditional knockout and cell lineage analysis in mice. Here we report a new multifunctional Cre/FLP dual reporter allele (R26(NZG)) that exhibits strong and apparently ubiquitous marker expression in embryos and adults. The reporter construct, which is driven by the CAG promoter, was knocked into the ROSA26 locus providing an open chromatin domain for consistent expression and avoiding site-of-integration effects often observed with transgenic reporters. R26(NZG) directs Cre-dependent nuclear-localized beta-galactosidase (beta-gal) expression, and can be converted into a Cre-dependent EGFP reporter (R26(NG)) by germline excision of the FRT-flanked nlslacZ cassette. Alternatively, germline excision of the floxed PGKNEO cassette in R26(NZG) generates an FLP-dependent EGFP reporter (R26(ZG)) that expresses beta-gal in FLP-nonexpressing cells. Finally, by the simultaneous use of both Cre and FLP deleters, R26(NZG) allows lineage relationships to be interrogated with greater refinement than is possible with single recombinase reporter systems.