Expression of foreign genes from retroviral vectors in mouse teratocarcinoma chimaeras

The formation of chimaeric mice from embryonic stem cells (EC and ES) carrying and exposing foreign genes is described. Two retroviral vectors were used to stably introduce genes, by virus infection and selection into EC and ES cells. In the first series EC cell clones were isolated that contained a single intact copy of the vector, which expressed the neomycin resistance gene (neo) from the 5' long terminal repeat (LTR). Following the formation of chimaeras with one of the clones, expression of the foreign gene was found in all chimaeric tissues examined. In the second series, a vector was used which contained the OK10 v-myc oncogene under the control of the 5' LTR as well as the neo gene expressed from an internal thymidine kinase (TK) promoter. ES cell clones were again isolated and used to form chimaeras. Although expression of the TK neo transcripts was maintained in the chimaeric tissues analysed, no expression of the v-myc transcripts from the 5' LTR was detected. These results show that genes can be introduced into mice, using clones of embryonic stem cells selected in vitro and that the expression of the genes can be maintained probably throughout development and in all tissues. The advantages this approach offers compared with DNA injection into eggs and the use of retroviruses as vectors for introducing genes into mice are discussed.