Lethal Deletion of the Complement Component C4 and Steroid 21-hydroxylase Genes in the Mouse H-2 Class III Region, Caused by Meiotic Recombination

A recombinant H-2 haplotype, designated aw18, was produced that underwent meiotic recombination in the Eα(I-E α chain)-Slp (sex-limited protein) interval of the H-2 class III region between B10.A (H-2a) and wild-derived B10.MOL-SGR (H-2wm7) strains. It appeared that the H-2aw18haplotype has a single, recessive, lethal mutation, since homozygotes for H-2aw18were not detected in progeny generated from the intercross of mice that were heterozygous for this H-2 haplotype. Nine newly established recombinant H-2 haplotypes, which arose from the heterozygous mice that resulted from a cross between common inbred H-2 haplotypes and the aw18 haplotype, allowed us to map the lethal gene to the class III region of the H-2 complex. Southern blot analysis indicated that the aw18 haplotype has a deletion of the C4 gene and a deletion of one of the steroid 21-hydroxylase genes. This result was confirmed by an immunodiffusion test that demonstrated the absence of production of the C4 protein in mice of haplotype H-2aw18. All data that were obtained supported the hypothesis that the meiotic, presumably unequal, recombination between homologous chromosomes of the H-2aand H-2wm7haplotypes caused the deletion of the C4 and the 21-hydroxylase genes.