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Analysis of MHC class II genes in the susceptibility to lupus in New Zealand mice

Rozzo, S. J.
Vyse, T. J.
David, C. S.
Palmer, E.
Kotzin, B. L.
Published in Journal of Immunology. 1999, vol. 162, no. 5, p. 2623-2630
Abstract Hybrids of New Zealand Black (NZB) and New Zealand White (NZW) mice spontaneously develop a disease similar to human systemic lupus erythematosus. MHC and non-MHC genes contribute to disease susceptibility in this murine model. Multiple studies have shown that the NZW H2z locus is strongly associated with the development of lupus-like disease in these mice. The susceptibility gene(s) within H2z is not known, but different lines of evidence have pointed to class II MHC genes, either H2-E or H2-A (Ez or Az in NZW). Recent studies from our laboratory showed that Ez does not supplant H2z in the contribution to lupus-like disease. In the present work we generated C57BL/10 (B10) mice transgenic for Aaz and Abz genes (designated B10.Az mice) and used a (B10.Az x NZB)F1 x NZB backcross to assess the contributions of Az genes to disease. A subset of backcross mice produced high levels of IgG autoantibodies and developed severe nephritis. However, no autoimmune phenotype was linked to the Az transgenes. Surprisingly, in the same backcross mice, inheritance of H2b from the nonautoimmune B10 strain was strongly linked with both autoantibody production and nephritis. Taken together with our previous Ez studies, the present work calls into question the importance of class II MHC genes for lupus susceptibility in this model and provides new insight into the role of MHC in lupus-like autoimmunity.
Keywords AnimalsAutoantibodies/biosynthesisCrosses, GeneticFemaleGenes, MHC Class IIGenetic Predisposition to DiseaseHistocompatibility Antigens Class II/geneticsImmunoglobulin G/biosynthesisLupus Erythematosus, Systemic/ geneticsLupus Nephritis/etiologyMiceMice, Inbred C57BLMice, Inbred NZBMice, Transgenic
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PMID: 10072504
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