Multiple lupus susceptibility loci map to chromosome 1 in BXSB mice.
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.
Hogarth
M B
MB
Rheumatology Section, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom.
Slingsby
J H
JH
Allen
P J
PJ
Thompson
E M
EM
Chandler
P
P
Davies
K A
KA
Simpson
E
E
Morley
B J
BJ
Walport
M J
MJ
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004198:Disease Susceptibility; D008040:Genetic Linkage / Q000276:immunology; D005819:Genetic Markers / Q000276:immunology*; D007668:Kidney / Q000473:pathology; D008181:Lupus Nephritis / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010641:Phenotype; D013154:Spleen / Q000473:pathology
D001323:Autoantibodies; D005819:Genetic Markers