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

J Clin Invest. 1996 Oct 15;98(8):1762-72. doi: 10.1172/JCI118975.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Antibodies, Antinuclear / physiology
  • Autoantibodies / biosynthesis*
  • Chromosome Mapping
  • Genetic Linkage*
  • Glycoproteins / immunology
  • Immunoglobulin G / biosynthesis*
  • Lupus Nephritis / genetics*
  • Lupus Nephritis / immunology
  • Mice
  • Mice, Inbred NZB
  • Phenotype


  • Antibodies, Antinuclear
  • Autoantibodies
  • Glycoproteins
  • Immunoglobulin G
  • glycoprotein gp70, murine serum