The targeting vector is designed to insert a minigene combining exons 23 and 24 in place of the endogenous exon 23. This minigene was modified to harbor a guanine to adenine substitution at amino acid 878, resulting in an arginine to histidine mutation (R878H), which corresponds to a R882H mutation commonly found in patients with acute myeloid leukemia (AML). A floxed STOP/neomycin cassette, including a splice acceptor and 3x SV40 polyA signals (saPGK-Neo-pA), was placed directly upstream of the modified minigene. (J:241153)