| First Author | Vyse TJ | Year | 1996 |
| Journal | J Immunol | Volume | 157 |
| Issue | 6 | Pages | 2719-27 |
| PubMed ID | 8805679 | Mgi Jnum | J:35434 |
| Mgi Id | MGI:82883 | Doi | 10.4049/jimmunol.157.6.2719 |
| Citation | Vyse TJ, et al. (1996) Backcross analysis of genes linked to autoantibody production in New Zealand White mice. J Immunol 157(6):2719-27 |
| abstractText | F-1 hybrids of New Zealand Black (NZB) and New Zealand White (NZW) mice are genetically predisposed to develop a lupus-like autoimmune disease characterized by IgG autoantibody production and an immune complex glomerulonephritis, Genes from both parental strains contribute to autoimmunity in the F-1 animal, NZW mice produce mostly non-pathogenic autoantibodies to ssDNA and histones as their major autoimmune trait, We studied the genetics of this trait in order to gain insight into the NZW contribution to F-1 disease, Genome-wide mapping of (NZW x BALB/c)F-1 x NZW backcross mice showed that four NZW non-MHC loci on chromosomes 1, 11, 16, and 19 were linked with Ige autoantibody production, Another NZW locus on chromosome 14 appeared to be selectively linked with IgG anti-histone Abs, In this backcross, contributions from the nonautoimmune BALB/c strain were also apparent, Heterozygosity for the BALB/c MHC (H2(d)) was linked with Ige autoantibody production. This influence of H2(d) is therefore similar to that seen in (NZW x NZB)F-1 mice, in which heterozygosity for H2(d) enhances autoantibody production and disease, Surprisingly, two non-MHC BALB/c loci were linked with IgM autoantibody levels, whereas no NZW loci had such an effect, Neither of these two loci have been previously linked with autoimmunity in lupus- prone mice, These data show that autoantibody production in NZW mice is a polygenic trait that is influenced by contributions from MHC and non-MHC genes, The results also support the hypothesis that NZW genes act to class-switch the autoantibody response, an effect that appears to contribute to disease in (NZB x NZW)F-1 mice. |
