Targeting of the Nrf-2 gene by homologous recombination. (A) Targeted disruption of one Nrf-2 allele. A representative Southern blot is shown hybridized with the Nrf-2 exon 2 probe (top) or a Neomycin resistance cDNA probe (bottom). The germline Hind III band of 4.0 kb is present in all clones. The 5.8-rearranged band, specific for homologous recombination, was present in about 60% of the clones. (B) Southern blot of tail DNA from the first F2 litter with controls. (C) Targeted disruption of both Nrf-2 alleles. A Southern blot is shown hybridized with the Nrf-2 exon 2 probe (top) or a hygromycin resistance cDNA probe (bottom). The second allele, disrupted by the hygromycin resistance gene, gives a 6.0-kb rearranged Hind III band and the appearance of a doublet on shorter exposures.