The Y chromosome from autoimmune BXSB/MpJ mice induces a lupus-like syndrome in (NZW x C57BL/6)F1 male mice, but not in C57BL/6 male mice.
The Y chromosome of the BXSB mouse has been shown to be responsible for the acceleration of lupus-like autoimmune syndrome in inbred BXSB mice and in their F1 hybrids with NZB or NZW mice. To further define the role of this as yet unidentified gene linked to the BXSB Y chromosome, designated Yaa (Y chromosome-linked autoimmune acceleration), the Y chromosome was transferred from the BXSB strain to nonautoimmune C57BL/6 (B6) mice. The effect of the Yaa gene on the autoantibody formation and the development of glomerulonephritis was investigated in B6 mice and in their F1 hybrids with NZW mice. The presence of the BXSB Y chromosome was not able to induce significant autoimmune responses in B6 mice. However, (NZW x B6)F1 males bearing the BXSB Y chromosome developed a severe lupus-like autoimmune syndrome, as documented by the production of anti-DNA antibodies and gp70-anti-gp70 immune complexes and the development of lethal lupus nephritis. Both sexes of (NZW x B6)F1 hybrids without the BXSB Y chromosome were essentially normal. Our results suggest that (a) the BXSB Y chromosome by itself is not sufficient to initiate autoimmune responses in nonautoimmune B6 mice, and (b) it is able to induce autoimmune responses in mice potentially capable of developing the disease, but whose autosomal abnormality by itself is not sufficient to develop autoimmune diseases.
Izui
S
S
Department of Pathology, University of Geneva, Switzerland.
Higaki
M
M
Morrow
D
D
Merino
R
R
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D000936:Antigen-Antibody Complex / Q000096:biosynthesis; D003433:Crosses, Genetic; D004247:DNA / Q000276:immunology; D005260:Female; D008040:Genetic Linkage; D005921:Glomerulonephritis / Q000209:etiology / Q000235:genetics / Q000401:mortality; D007108:Immune Tolerance; D007113:Immunity, Innate; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D012727:Sex Characteristics; D014998:Y Chromosome / Q000276:immunology* / Q000502:physiology
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D004247:DNA