Studies of consomic mice bearing the Y chromosome of the BXSB mouse.
Previous studies have demonstrated that the Y chromosome of the BXSB mouse can lead to accelerated autoimmunity in inbred BXSB mice and in F1 hybrids. To additionally study the effects of the BXSB-Y, we have studied three sets of Y-consomic mice, NZB.BXSB-Y, NZW.BXSB-Y, and CBA/J.BXSB-Y, each consisting of background genes from the non-BXSB parent and the Y chromosome from the BXSB mouse. The effect of the BXSB-Y on autoantibody production, immunopathology, and survival was assessed. We found that the CBA/J.BXSB-Y mice showed few differences from control CBA/J males. In contrast, NZW.BXSB-Y males had accelerated renal and cardiac disease and early death, resembling that previously reported for (NZW X BXSB)F1 mice. NZB.BXSB-Y males had accelerated anti-erythrocyte autoantibodies but not accelerated anti-DNA. They lived almost as long as NZB mice. The presence of the BXSB-Y in all of the consomic mice was confirmed by crossing the consomic mice with BXSB females and demonstrating accelerated disease in the male offspring. This study demonstrates that the BXSB-Y chromosome autoimmune accelerating factor does not act alone but operates through other genes, and that the effects on different genetic backgrounds are different. The studies have implications for human lupus; they also provide a basis for future molecular biology studies of the BXSB-Y and the genes upon which it acts.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D003298:Coombs Test; D003327:Coronary Disease / Q000235:genetics / Q000503:physiopathology; D004277:DNA, Single-Stranded / Q000276:immunology; D005260:Female; D007668:Kidney / Q000473:pathology; D008136:Longevity; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008814:Mice, Inbred NZB; D008815:Mice, Inbred Strains / Q000235:genetics* / Q000276:immunology; D013163:Splenomegaly / Q000235:genetics; D014998:Y Chromosome
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D004277:DNA, Single-Stranded