Cyp2d^tm1.2Arte

A targeting construct replaced exons 4 and 5 of Cyp2d22 with an FRT site, 9 kb human CYP2D6 promoter, 4.4 kb CYP2D6 genomic DNA, polyadenylation sequence, loxP site, neomycin resistance cassette. The human sequence from RP11-142E17 contains the following polymorphisms: the nucleotide transitions 1023C to T and 2850C to T(leading to the amino acid exchanges T107I and R296C in exon 2 and 6, respectively) and a gene conversion to CYP2D7 in exon 9 (associated with the amino acid exchanges P469A, T470A, H478S, G479A, F481V, A482S, and S486T). A second targeting cassette inserted a hygromycin resistance cassette, loxP site, FRT site, splice acceptor polyA sequence, and ZsGreen reporter gene into intron 4 of Cyp2d26. Cre-mediated recombination removed exons 1 through 3 of Cyp2d22 through exon 5 of Cyp2d26 as well as both selection cassettes. Flp-mediated recombination removed the human sequence. (J:241123)