Genetic linkage of IgG autoantibody production in relation to lupus nephritis in New Zealand hybrid mice.
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.
Vyse
T J
TJ
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.
Drake
C G
CG
Rozzo
S J
SJ
Roper
E
E
Izui
S
S
Kotzin
B L
BL
D000483:Alleles; D000818:Animals; D000974:Antibodies, Antinuclear / Q000502:physiology; D001323:Autoantibodies / Q000096:biosynthesis*; D002874:Chromosome Mapping; D008040:Genetic Linkage; D006023:Glycoproteins / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis*; D008181:Lupus Nephritis / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008814:Mice, Inbred NZB; D010641:Phenotype
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D006023:Glycoproteins; D007074:Immunoglobulin G; C033589:glycoprotein gp70, murine serum