A targeting vector was designed to insert a cre/ERT2-SV40 polyA cassette followed by an FRT5-flanked pSV40-NeoR-pA cassette into the translational start site of the FBJ osteosarcoma oncogene gene (Fos). The targeting event displaced the introns and coding regions and replaced the endogenous 3' UTRs (which contribute to mRNA destabilization and to Arc mRNA dendritic trafficking) with an exogenous SV40 polyadenylation signal (to promote high-level expression). All sequences 5' to the translational start site are retained. The construct was electroporated into R1 embryonic stem (ES) cells and correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were bred to germline-active GFP-FlpO transgenic mice to delete the FRT5-flanked pSV40-NeoR-pA cassette.