Genetic studies of autoimmunity in New Zealand mice. IV. Contribution of NZB and NZW genes to the spontaneous occurrence of retroviral gp70 immune complexes in (NZB X NZW)F1 hybrid and the correlation to renal disease.

We designed a polyethylene glycol precipitation method for detecting retroviral gp70-anti-gp70 immune complexes (gp70 IC) in the circulation of mice. To determine the genetic contribution of NZB and NZW strains to the spontaneous occurrence of circulating gp70 IC in NZB X NZW (B/W)F1 hybrids, we measured these IC in female NZB, NZW, (NZB X NZW)F1 (B/W F1), B/W F1 X NZW backcross, and B/W F1 X NZB backcross mice. The highest amounts of gp70 IC were found in B/W F1 and the lowest in NZW mice, and the order of the average serum levels was B/W F1, B/W F1 X NZB, B/W F1 X NZW, NZB, and NZW. Genetic analyses suggested that two major dominant genes, one from NZB and the other from NZW, are involved in the formation of these gp70 IC. A single dominant gene of NZB strain determines the formation of these IC, and the magnitude is to a great degree modified (intensified) by the NZW gene. In addition, statistical analyses of data obtained in the studies of B/W F1 X NZW backcrosses suggested the presence of one additional dominant NZB gene that also regulates the magnitude of gp70 IC formation in concert with the other NZB gene. Since all these New Zealand mice share a high serum level of free gp70, the formation of gp70 IC represents the gene action on the production of anti-gp70 antibodies. Linkage studies showed that both of the major NZB and NZW genes are loosely linked to the H-2 complex but not to either the Mup-1 or coat color gene loci examined. The incidence of proteinuria correlated well with the serum level of gp70 IC in both B/W F1 X NZW and B/W F1 X NZB backcross mice.