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Genetic linkage of IgG autoantibody production in relation to lupus nephritis in New Zealand hybrid mice

Vyse, T. J.
Drake, C. G.
Rozzo, S. J.
Roper, E.
Kotzin, B. L.
Published in The Journal of clinical investigation. 1996, vol. 98, no. 8, p. 1762-1772
Abstract F1 hybrids of New Zealand black (NZB) and New Zealand white (NZW) mice are a model of human systemic lupus erythematosus. These mice develop a severe immune com-plex-mediated nephritis, in which antinuclear autoantibodies are believed to play the major role. We used a genetic analysis of (NZB x NZW)F1 x NZW backcross mice to provide insight into whether different autoantibodies are subject to separate genetic influences and to determine which autoantibodies are most important in the development of lupus-like nephritis. The results showed one set of loci that coordinately regulated serum levels of IgG antibodies to double-stranded DNA, single-stranded DNA, total histones, and chromatin, which overlapped with loci that were linked to the production of autoantibodies to the viral glycoprotein, gp70. Loci linked with anti-gp70 compared with antinuclear antibodies demonstrated the strongest linkage with renal disease, suggesting that autoantibodies to gp70 are the major pathogenic antibodies in this model of lupus nephritis. Interestingly, a distal chromosome 4 locus, Nba1, was linked with nephritis but not with any of the autoantibodies measured, suggesting that it contributes to renal disease at a checkpoint distal to autoantibody production.
Keywords AllelesAnimalsAntibodies, Antinuclear/physiologyAutoantibodies/ biosynthesisChromosome MappingGlycoproteins/immunologyImmunoglobulin G/ biosynthesisLinkage (Genetics)Lupus Nephritis/ genetics/immunologyMiceMice, Inbred NZBPhenotype
PMID: 8878426
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VYSE, T. J. et al. Genetic linkage of IgG autoantibody production in relation to lupus nephritis in New Zealand hybrid mice. In: The Journal of clinical investigation, 1996, vol. 98, n° 8, p. 1762-1772. doi: 10.1172/JCI118975

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Deposited on : 2010-08-27

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