Experiment
A congenic line (referred to by authors as ZWD/8) carrying an NZB-derived H2 locus on the NZW genetic backbground was created. Parental strain NZB spontaneously develops autoantibodies and glomerulonephritis similar to human lupus nephritis. ZWD/8 does not exhibit autoimmune abnormalities, similar to NZW. Female (NZB x ZWD/8)F1 and (NZB/NZW)F1 animals were analyzed.
Four loci, Ads1 (anti dsDNA antibody 1) through Ads4, are postulated to control the level of double-stranded DNA (dsDNA) in NZB and NZW strain mice and their crosses. Dominant alleles from NZB at the independently segregating Ads1 and Ads2 loci cause a high level of IgM with anti-dsDNA specificity; recessive alleles from NZW produce very little anti-dsDNA antibody. Dominant alleles at the independently segregating Ads3 and Ads4 loci occur in NZW and cause conversion of the anti-dsDNA antibodies of (NZB x NZW)F1 mice from IgM to IgG; recessive alleles from NZB allow production of IgM antibodies. (NZB x NZW)F1 mice thus have high levels of anti-dsDNA antibodies, mostly composed of IgG. Ads1 is probably linked to H2 but not within the H2 complex; Ads3 is probably within the H2 complex. The locations of Ads2 and Ads4 are not known.
Near the H2 locus on mouse Chromosome 17, a dominant NZB-derived locus named Agp1 (anti gp70 immune complex 1) and a dominant NZW-derived locus named Agp3 contributes to increased anti-gp70. It is possible that the Ads and Agp loci are identical or are parts of the same complex, which also may include the Lpn1 and Lpn2 loci, affecting incidence of lupus nephritis in NZ, NXW, and their crosses.
Analysis Tools