Genetic studies of autoimmunity in New Zealand mice. III. Associations among anti-DNA antibodies, NTA, and renal disease in (NZB x NZW)F1 x NZW backcross mice.

Abstract

Abstract Anti-dsDNA and anti-ssDNA antibodies were measured in female NZB, NZW, B/W F1, and the F1 x NZW back-cross mice. The production of these 2 antibodies in the B/W F1 hybrids seems to depend on the action of genes from both parental NZB and NZW strains, since neither of the parental strains showed so high an incidence and serum level as occurs in the F1 hybrids. The data from the B/W F1 × NZW backcross mice suggested that the NZB strain contributes 2 genes or clusters of more genes to the occurrence of anti-dsDNA antibodies in the F1 hybrids. The production of anti-ssDNA antibodies appeared to be under multifactorial control. However, a significant association between these 2 types of antibodies suggested the presence of a common gene. There was a significant correlation between the quantities of NTA and both anti-dsDNA and anti-ssDNA antibodies. In particular, NTA quantitatively correlated well with the anti-dsDNA antibodies only in the group of progeny positive for anti-dsDNA antibodies. A highly significant correlation was observed between the occurrences of anti-dsDNA antibodies and proteinuria in the backcrosses throughout all the ages tested. The correlation was inconstant between the anti-ssDNA antibodies and proteinuria. An accelerated onset and the highest incidence of proteinuria occurred in the progeny with coincidence of NTA and anti-dsDNA antibodies. This is strikingly similar to our previous findings of the correlation among NTA, retrovirus gp70 immune complexes, and proteinuria in the same backcrosses. At least 1 each of anti-dsDNA and anti-ssDNA genes appeared to be linked to the H-2 complex.