A targeting vector was designed with a loxP-flanked STOP cassette upstream of the open reading frame of the simian Diphtheria Toxin Receptor (DTR; from simian hbEGF cDNA (base pair 56-682)). The loxP-flanked region contains two SV40 polyA signals, an frt-flanked neomycin resistance gene, and a transcriptional STOP cassette. This construct was inserted into the Gt(ROSA)26Sor locus via electroporation of C57BL/6-derived Bruce4 ES embryonic stem (ES) cells. Widespread expression of DTR is blocked by an upstream loxP-flanked STOP sequence. When bred to Cre recombinase-expressing mice, the STOP sequence is deleted in tissues where Cre is present, permitting DTR expression. Cells expressing DTR are rendered susceptible to ablation following Diphtheria toxin administration.