Linkage of a major quantitative trait locus to Yaa gene-induced lupus-like nephritis in (NZW x C57BL/6)F1 mice.
In the present study, we mapped the major quantitative trait loci (QTL) differing between the NZW and C57BL/6 inbred strains of mice by making use of (NZW x C57BL/6.Yaa)F1 mice, a model in which the lupus-like autoimmune syndrome observed in male mice is associated with the presence of an as yet unidentified Y chromosome-linked autoimmune acceleration gene, Yaa. Linkage analysis of 126 C57BL/6 x (NZW x C57BL/6.Yaa)F1 backcross males provided evidence for a major QTL on chromosome 7 controlling both the severity of glomerulonephritis and the production of IgG anti-DNA autoantibody and retroviral gp70-anti-gp70 immune complexes. Two additional QTL of C57BL/6 origin on chromosome 17 had no apparent individual effects, but showed strong epistatic interaction with chromosome 7 QTL for disease severity and anti-DNA autoantibody production. Our data also identified on chromosome 13 a QTL of NZW origin with a major effect on the level of gp70, and showing an additive effect with the chromosome 7 QTL on the level of gp70 immune complexes. Our study thus provides a model to dissect the complex genetic interactions that result in manifestations of murine lupus-like disease.
Santiago
M L
ML
INSERM U399, Université de la Méditerranée, Marseille, France.
Mary
C
C
Parzy
D
D
Jacquet
C
C
Montagutelli
X
X
Parkhouse
R M
RM
Lemoine
R
R
Izui
S
S
Reininger
L
L
D000818:Animals; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology; D002874:Chromosome Mapping; D008040:Genetic Linkage; D008181:Lupus Nephritis / Q000235:genetics* / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019655:Quantitative Trait, Heritable; D014998:Y Chromosome
D001323:Autoantibodies