Genetically modified somatic cells of a non-human animal are provided that are engineered to contain a self-excisable, recombinase expression cassette comprising a site-specific recombinase gene operably linked to an ES cell-specific promoter. Compositions and methods for producing a genetically modified, cloned non-human animal that is free of a selective marker gene and a recombinase gene are provided, wherein a targeting construct comprising a self-excisable recombinase gene operably linked to an ES cell-specific promoter is introduced into differentiated somatic cells. The genetically modified genome of the somatic cells is transferred into an enucleated host oocyte. The artificially created zygote is then cultured in vitro until the blastocyst embryonic stage and subsequently implanted into a uterus of a surrogate mother to form a genetically modified, cloned non-human animal free of selective marker and recombinase genes.
