Spatial and temporal expression of the Cre gene under the control of the MMTV-LTR in different lines of transgenic mice

Cre-loxP based gene deletion approaches hold great promise to enhance our u nderstanding of molecular pathways controlling mammary development and brea st cancer. We reported earlier the generation of transgenic mice that expre ss the Cre recombinase under the control of the mouse mammary tumor virus ( MMTV) long terminal repeat (LTR). These mice have become a valuable researc h tool to delete genes specifically in the mammary gland, other secretory o rgans, and the female germline. We have now characterized in depth the expr ession of the MMTV-Cre transgene using the ROSA26-lox-Stop-lox-LacZ reporte r strain to determine the temporal and spatial activation of Cre on the lev el of single cells. Our results show that MMTV-mediated Cre-activation is r estricted to specific cell types of various secretory tissues and the hemat opoietic system. Secondly, the timing of Cre expression varies between tiss ues and cell types. Some tissues express Cre during embryonic development, while other selected cell types highly activate Cre around puberty, suggest ing a strong influence of steroid hormones on the transcriptional activatio n of the MMTV-LTR. Thirdly, Cre expression in the female germline is restri cted to individual mouse lines and is therefore dependent on the site of in tegration of the transgene. Information provided by this study will guide t he researcher to those cell types and developmental stages at which a pheno type can be expected upon deletion of relevant genes.