Linkage of a major quantitative trait locus to Yaa gene-induced lupus-likenephritis in (NZW x C57BL/6)F1 mice

In the present study, we mapped the major quantitative trait loci (QTL) dif fering 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 synd rome observed in male mice is associated with the presence of an as yet uni dentified Y chromosome-linked autoimmune acceleration gene, Yaa. Linkage an alysis of 126 C57BL/6 x (NZW x C578L/6.Yaa)F1 backcross males provided evid ence for a major QTL on chromosome 7 controlling both the severity of glome rulonephritis and the production of IgG anti-DNA autoantibody and retrovira l gp70-anti-gp70 immune complexes. Two additional QTL of C57BL/6 origin on chromosome 17 had no apparent individual effects, but showed strong epistat ic interaction with chromosome 7 QTL for disease severity and anti-DNA auto antibody 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 e ffect with the chromosome 7 QTL on the revel of gp70 immune complexes. Our study thus provides a model to dissect the complex genetic interactions tha t result in manifestations of murine lupus-like disease.