A targeting vector was designed to insert a loxP site and an FRT-flanked hygromycin resistance (hygro) cassette upstream of the first coding exon of the absent in melanoma 2 (Aim2) gene. A second targeting vector was used to insert a second loxP site and an FRT-flanked neomycin resistance (neo) cassette upstream of the first coding exon of the interferon activated gene 205 (Ifi205) gene. Flp-mediated recombination removed the FRT-flanked neo and hygro cassettes. Cre-mediated recombination removed the loxP-flanked region deleting the mouse ALR (Aim2-like receptor) locus, a 570 kilobase region on chromosome 1 spanning 13 genes from Aim2 to Ifi205. The absence of transcript expression was confirmed by RT-PCR on macrophages and embryonic fibroblasts. Western blot confirmed that no protein was expressed in mutant mice. (J:234263)