Use of ERT2-iCre-ERT2 for conditional transgenesis

We examined the use of ERT2-iCre-ERT2 (Cre2ERT2), a tamoxifen-regulated form of Cre that has been described to have a background activity lower than that of other tamoxifen-regulated Cre constructs, for establishing performant conditional deleter mouse lines. Cre2ERT2 was inserted by homologous recombination into the Rosa26 locus. These mice were mated with R26R Cre-reporter mice. No recombination could be observed in the progenies in the absence of tamoxifen treatment. Tamoxifen treatment at E13-14 led to a high level, albeit variable, recombination in most of the tissues examined: liver, heart, kidney, brain, lung etc. Treatment of adult animals also induced recombination in these tissues, although at a lower level. Northern blot and qPCR studies suggested that these differences are not linked to significant variations of the level of expression of Cre2ERT2. Thus, Cre2ERT2 appears to be a good alternative to existing modulatable Cre systems, displaying a lack of background activity and a high-level inducibility in vivo.