Identification of intervals on chromosomes 1, 3, and 13 linked to the development of lupus in BXSB mice.
OBJECTIVE
To identify intervals containing systemic lupus erythematosus (SLE) susceptibility alleles in the BXSB strain of mice.


METHODS
We analyzed 286 (B10 x [B10 x BXSB]F1) backcross mice for a range of phenotypic traits associated with the development of SLE in BXSB mice. The mice were genotyped using 93 microsatellite markers, and the linkage of these markers to disease was studied by extreme-phenotype and quantitative trait locus analysis.


RESULTS
The disease phenotype in these backcross mice was less severe than that in BXSB mice. However, antinuclear antibody production was increased compared with the parental strain. We identified 4 areas of genetic linkage to disease on chromosome 1 (Bxs1-4), 1 on chromosome 3 (Bxs5), and another interval on chromosome 13 which were associated with various aspects of the phenotype. Bxs4 and Bxs5 are located in regions not previously linked to disease in other models of SLE.


CONCLUSIONS
SLE in the BXSB mouse model has a complex genetic basis and involves at least 5 distinct intervals located on chromosomes 1 and 3. There is evidence that different intervals affect particular aspects of the SLE phenotype.
Haywood
M E
ME
Imperial College School of Medicine, London, UK.
Hogarth
M B
MB
Slingsby
J H
JH
Rose
S J
SJ
Allen
P J
PJ
Thompson
E M
EM
Maibaum
M A
MA
Chandler
P
P
Davies
K A
KA
Simpson
E
E
Walport
M J
MJ
Morley
B J
BJ
D000483:Alleles; D000818:Animals; D000974:Antibodies, Antinuclear / Q000235:genetics; D002875:Chromosomes / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1; D002882:Chromosomes, Human, Pair 13; D002893:Chromosomes, Human, Pair 3; D004247:DNA / Q000276:immunology; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains
D000974:Antibodies, Antinuclear; D004247:DNA