A double targeting strategy is used to remove a 250 kb region that includes the six alcohol dehydrogenase genes. One targeting construct was designed to insert a loxP site and hygromycin resistance gene into intron 3 the Adh7 gene, a second targeting construct was designed to insert a neomycin resistance gene and loxP site into intron 4 of the Adh5 gene. All six Adh genes are located on Chr3 in the following order: Adh7, Adh1, Adh6a, Adh6b, Adh4, Adh5; no other genes are located in this region. Cre-mediated recombination removed the floxed region and the neomycin and hygromycin cassetes. (J:271228)