A novel susceptibility locus on chromosome 2 in the (New Zealand Black × New Zealand White)F1 hybrid mouse model of systemic lupus erythematosus

Ziaur S.M. Rahman, Soe Kyaw Tin, Pia Nina L. Buenaventura, Chiu Han Ho, Eric P.H. Yap, Rita Y.Y. Yong, Dow Rhoon Koh

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Abstract

Systemic lupus erythematosus (SLE) is inherited as a complex polygenic trait. (New Zealand Black (NZB) × New Zealand White (NZW)) F1 hybrid mice develop symptoms that remarkably resemble human SLE, but (NZB × PL/J)F1 hybrids do not develop lupus. Our study was conducted using (NZW × PL/J)F1 × NZB (BWP) mice to determine the effects of the PL/J and the NZW genome on disease. Forty-five percent of BWP female mice had significant proteinuria and 25% died before 12 mo of age compared with (NZB × NZW)F1 mice in which >90% developed severe renal disease and died before 12 mo. The analysis of BWP mice revealed a novel locus (X2 = 25.0; p < 1 × 10-6; log of likelihood = 6.6 for mortality) designated Wbwl on chromosome 2, which apparently plays an important role in the development of the disease. We also observed that both H-2 class II (the u haplotype) and TNF-α (TNF allele) appear to contribute to the disease. A suggestive linkage to proteinuria and death was found for an NZW allele (designated Wbw2) telomeric to the H-2 locus. The NZW allele that overlaps with the previously described locus Sle1c at the telomeric part of chromosome 1 was associated with antinuclear autoantibody production in the present study. Furthermore, the previously identified Sle and Lbw susceptibility loci were associated with an increased incidence of disease. Thus, multiple NZW alleles including the Wbwl allele discovered in this study contribute to disease induction, in conjunction with the NZB genome, and the PL/J genome appears to be protective.

Original languageEnglish (US)
Pages (from-to)3042-3049
Number of pages8
JournalJournal of Immunology
Volume168
Issue number6
StatePublished - Mar 15 2002

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Rahman, Z. S. M., Tin, S. K., Buenaventura, P. N. L., Ho, C. H., Yap, E. P. H., Yong, R. Y. Y., & Koh, D. R. (2002). A novel susceptibility locus on chromosome 2 in the (New Zealand Black × New Zealand White)F1 hybrid mouse model of systemic lupus erythematosus. Journal of Immunology, 168(6), 3042-3049.