Use of the Cre-loxP strategy to delete an entire subfamily of P450 genes. The individual genes are denoted by rectangles and the loxP sites by triangles. The sequence of the locus can be obtained from the public or Celera database, and bacterial artificial chromosome clones that flank the complete cluster of genes can be chosen. LoxP sites are introduced by use of in vivo recombination to generate constructs for transfection into embryonic stem (ES) cells . This is carried out by two consecutive transfections into ES cells followed by treatment with Cre recombinase to delete the DNA between the loxP sites. The ES cells can then be used to make a knockout mouse.