Linkage of a major quantitative trait locus to Yaa gene-induced lupus-like nephritis in (NZW × C57BL/6)F1 mice
✍ Scribed by Marie-Laure Santiago; Charles Mary; Daniel Parzy; Chantal Jacquet; Xavier Montagutelli; R. Michael E. Parkhouse; Robert Lemoine; Shozo Izui; Luc Reininger
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 152 KB
- Volume
- 28
- Category
- Article
- ISSN
- 0014-2980
No coin nor oath required. For personal study only.
✦ Synopsis
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 × 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 × (NZW × 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.