Multiple lupus susceptibility loci map to chromosome 1 in BXSB mice

MB Hogarth, JH Slingsby, PJ Allen, EM Thompson, P Chandler, KA Davies, E Simpson, Bernard J Morley, MJ Walport

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Abstract

BXSB mice spontaneously develop a lupus-like syndrome that is accelerated by the Yaa gene (Y-linked autoimmune accelerator). We studied the phenotype of disease in (B10 x BXSB)F1 and (BXSB x (B10 x BXSB)F1) backcross mice and genotyped 224 backcross animals to allow a microsatellite-based genome-wide linkage analysis to be conducted. In the backcross population, three intervals on chromosome 1 showed significant linkage to disease, suggesting that multiple loci contribute to the production of autoimmune disease. D1Mit5 at 32.8 cM was linked to development of nephritis (chi(2) = 15.68, p = 7.5 x 10(-5)), as was D1Mit12 at 63.1 cM (chi(2) = 20.17, p = 7.1 x 10(-6)). D1Mit403 at 100 cM was linked to anti-dsDNA Ab production (chi(2) = 17.28, p = 3.2 x 10(-5)). Suggestive linkages to antinuclear Abs and nephritis were identified on chromosome 3, to splenomegaly on chromosome 4, and to anti-ssDNA Ab production on chromosome 10. Chromosome 4 and the telomeric region of chromosome 1 have previously been linked to disease in other mouse models of systemic lupus erythematosus; however, the centromeric regions of chromosome 1 and chromosomes 3 and 10 are unique to BXSB. This implies that, though some loci may be common to a number of mouse models of lupus, different clusters of disease genes confer disease susceptibility in different strains of mice.
Original languageEnglish
Pages (from-to)2753-2761
Number of pages9
JournalThe Journal of Immunology
Volume161
Publication statusPublished - Sep 1998

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    Hogarth, MB., Slingsby, JH., Allen, PJ., Thompson, EM., Chandler, P., Davies, KA., Simpson, E., Morley, B. J., & Walport, MJ. (1998). Multiple lupus susceptibility loci map to chromosome 1 in BXSB mice. The Journal of Immunology, 161, 2753-2761.