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Multiple lupus susceptibility loci map to chromosome 1 in BXSB mice


Reference:

Hogarth, M., Slingsby, J., Allen, P., Thompson, E., Chandler, P., Davies, K., Simpson, E., Morley, B. J. and Walport, M., 1998. Multiple lupus susceptibility loci map to chromosome 1 in BXSB mice. The Journal of Immunology, 161, pp. 2753-2761.

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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.

Details

Item Type Articles
CreatorsHogarth, M., Slingsby, J., Allen, P., Thompson, E., Chandler, P., Davies, K., Simpson, E., Morley, B. J. and Walport, M.
DepartmentsUniversity Administration & Central Services > Vice-Chancellor's Office
RefereedYes
StatusPublished
ID Code19285

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