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

Research output: Contribution to journalArticle

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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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Chromosomes, Human, Pair 1
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 4
Chromosomes, Human, Pair 3
Nephritis
Y-Linked Genes
Disease Susceptibility
Splenomegaly
Multigene Family
Systemic Lupus Erythematosus
Microsatellite Repeats
Autoimmune Diseases
Genome
Phenotype
Population

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

Multiple lupus susceptibility loci map to chromosome 1 in BXSB mice. / Hogarth, MB; Slingsby, JH; Allen, PJ; Thompson, EM; Chandler, P; Davies, KA; Simpson, E; Morley, Bernard J; Walport, MJ.

In: The Journal of Immunology, Vol. 161, 09.1998, p. 2753-2761.

Research output: Contribution to journalArticle

Hogarth, MB, Slingsby, JH, Allen, PJ, Thompson, EM, Chandler, P, Davies, KA, Simpson, E, Morley, BJ & Walport, MJ 1998, 'Multiple lupus susceptibility loci map to chromosome 1 in BXSB mice', The Journal of Immunology, vol. 161, pp. 2753-2761.
Hogarth MB, Slingsby JH, Allen PJ, Thompson EM, Chandler P, Davies KA et al. Multiple lupus susceptibility loci map to chromosome 1 in BXSB mice. The Journal of Immunology. 1998 Sep;161:2753-2761.
Hogarth, MB ; Slingsby, JH ; Allen, PJ ; Thompson, EM ; Chandler, P ; Davies, KA ; Simpson, E ; Morley, Bernard J ; Walport, MJ. / Multiple lupus susceptibility loci map to chromosome 1 in BXSB mice. In: The Journal of Immunology. 1998 ; Vol. 161. pp. 2753-2761.
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AU - Slingsby, JH

AU - Allen, PJ

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AU - Simpson, E

AU - Morley, Bernard J

AU - Walport, MJ

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N2 - 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.

AB - 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.

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