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

Stephen J. Rozzo, Timothy J. Vyse, Chella S. David, Ed Palmer, Shozo Izui, Brian L. Kotzin

Research output: Contribution to journalArticle

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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 H2(z) locus is strongly associated with the development of lupus-like disease in these mice. The susceptibility gene(s) within H2(z) is not known, but different lines of evidence have pointed to class II MHC genes, either H2-E or H2-A (E(z) or A(z) in NZW). Recent studies from our laboratory showed that E(z) does not supplant H2(z) in the contribution to lupus-like disease. In the present work we generated C57BL/10 (B10) mice transgenic for Aa(z) and Ab(z) genes (designated B10.A(z) mice) and used a (B10.A(z) x NZB)F1 x NZB backcross to assess the contributions of A(z) 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 A(z) transgenes. Surprisingly, in the same backcross mice, inheritance of H2(b) from the nonautoimmune B10 strain was strongly linked with both autoantibody production and nephritis. Taken together with our previous E(z) 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.

Original languageEnglish (US)
Pages (from-to)2623-2630
Number of pages8
JournalJournal of Immunology
Volume162
Issue number5
StatePublished - Mar 1 1999

Fingerprint

MHC Class II Genes
New Zealand
Nephritis
Autoantibodies
Genes
Disease Susceptibility
Autoimmunity
Transgenes
Systemic Lupus Erythematosus
Transgenic Mice
Immunoglobulin G
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

Rozzo, S. J., Vyse, T. J., David, C. S., Palmer, E., Izui, S., & Kotzin, B. L. (1999). Analysis of MHC class II genes in the susceptibility to lupus in New Zealand mice. Journal of Immunology, 162(5), 2623-2630.

Analysis of MHC class II genes in the susceptibility to lupus in New Zealand mice. / Rozzo, Stephen J.; Vyse, Timothy J.; David, Chella S.; Palmer, Ed; Izui, Shozo; Kotzin, Brian L.

In: Journal of Immunology, Vol. 162, No. 5, 01.03.1999, p. 2623-2630.

Research output: Contribution to journalArticle

Rozzo, SJ, Vyse, TJ, David, CS, Palmer, E, Izui, S & Kotzin, BL 1999, 'Analysis of MHC class II genes in the susceptibility to lupus in New Zealand mice', Journal of Immunology, vol. 162, no. 5, pp. 2623-2630.
Rozzo SJ, Vyse TJ, David CS, Palmer E, Izui S, Kotzin BL. Analysis of MHC class II genes in the susceptibility to lupus in New Zealand mice. Journal of Immunology. 1999 Mar 1;162(5):2623-2630.
Rozzo, Stephen J. ; Vyse, Timothy J. ; David, Chella S. ; Palmer, Ed ; Izui, Shozo ; Kotzin, Brian L. / Analysis of MHC class II genes in the susceptibility to lupus in New Zealand mice. In: Journal of Immunology. 1999 ; Vol. 162, No. 5. pp. 2623-2630.
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