Agp1^NZB
QTL Variant Detail

Summary

• QTL variant: Agp1^NZB
• Name: anti gp70 immune complex 1; NZB
• MGI ID: MGI:3620205
• QTL: Agp1 Location: unknown Genetic Position: Chr17, Syntenic

Variant origin

• Strain of Specimen: NZB

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This locus confers increased anti-gp70 immune complex formation compared to NZW. (J:6920)
• Inheritance: Dominant

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:7111

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.

J:6920

Inbred strain NZB spontaneously develops autoantibodies and glomerulonephritis similar to human lupus nephritis, whereas inbred strain NZW does not. Analysis of 123 (NZB x NZW)F1 x NZW and 113 (NZB x NZW)F1 x NZB female backcross animals reveal 2 dominant H2- linked loci associated with anti-gp70 immune complex formation. Agp1 (anti gp70 immune complex 1) is derived from the NZB genetic background whereas Agp2 (anti gp70 immune complex 2) is derived from the NZW genetic background. Loose linkage between Agp1 and H2 is estimated at 25.2 cM. The location of Agp2 is estimated to be approximately 31 cM from H2. Agp2 may act to intensify formation of gp70 immune complexes in concert with Agp1. A separate unlinked and yet unidentified locus affecting the magnitude of gp70 immune complex formation was hypothesized to exist.

References

• Original: J:6920 Maruyama N, et al., Genetic studies of autoimmunity in New Zealand mice. IV. Contribution of NZB and NZW genes to the spontaneous occurrence of retroviral gp70 immune complexes in (NZB X NZW)F1 hybrid and the correlation to renal disease. J Immunol. 1983 Feb;130(2):740-6
• All: 1 reference(s)