Lupus Susceptibility Loci in New Zealand Mice

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 21; pp. 10168 - 10172
• Main Authors: Kono, Dwight H., Burlingame, Rufus W., Owens, Dan G., Kuramochi, Akiko, Balderas, Robert S., Balomenos, Dimitrios, Theofilopoulos, Argyrios N.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 11-10-1994; National Acad Sciences; National Academy of Sciences
• Subjects: Animals; Blood; Chromosome Mapping; Chromosomes; Crosses, Genetic; Disease; Disease susceptibility; Female; Genes; Genetic Linkage; Genetic loci; Genetic Markers; Genetic Predisposition to Disease; Genetics; Genome; Immunity (Disease); Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Medical genetics; Medical research; Mice; Mice, Inbred Strains; Mortality; New Zealand; Rodents; Spleen; Splenomegaly; Systemic lupus erythematosus; New Zealand
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.21.10168

Susceptibility to systemic lupus erythematosus has been unequivocally established to be an inherited trait, but the exact genes and how they confer susceptibility remain largely unknown. In this study of (NZB x NZW)F2intercross mice, we used linkage analysis of markers covering >90% of the autosomal genome and identified eight susceptibility loci (Lbw1 to -8, chromosomes 17, 4-7, 18, 1, 11, respectively) associated with antichromatin autoantibody production, glomerulonephritis, and/or mortality. Only one locus, the major histocompatibility complex, was linked to all three traits. Two other loci were associated with both glomerulonephritis and mortality, whereas the remaining loci were linked to one of the above traits. Two additional loci (Sbw1 and -2) that contributed to splenomegaly were also identified. The Sbw2 locus mapped to the identical region as Lbw2, a locus on chromosome 4 linked to glomerulonephritis and mortality, suggesting a single locus with pleiotropic effects. The results indicate that the immunopathologic features of lupus are affected by distinct, but additive, genetic contributions. Studies to determine the nature of the genes associated with these loci should help define the genetic mechanisms involved in this systemic autoimmune disease.