Selective cell ablation in the mammary gland of transgenic mice

We have generated transgenic mice which express the gene encoding E. coli nitroreductase (NTR) specifically in the luminal epithelial cells of the mammary gland and shown that administration of the anti-tumour drug CB1954 rapidly and selectively kills these cells. Owing to the ease of control of NTR-mediated cell ablation, we anticipate that this system will supercede herpes simplex virus type 1 thymidine kinase. There are widespread potential applications for this approach in the dissection of complex cellular interactions during development and in the adult organism. The present transgenic model also has important applications for the study in vivo of novel prodrugs that can be selected for variable degrees of bystander effects. Such studies will have particular significance for those groups advocating the use of NTR as an appropriate enzyme for gene-directed enzyme prodrug therapy by providing models of a wide range of human disease for mechanistic and therapeutic experimentation. The model described in this work has potential for the examination of mammary carcinogenesis and its modulation through manipulation of the size of the target cell populations.