Implication of allelic polymorphism of osteopontin in the development of lupus nephritis in MRL/lpr mice

Tatsuhiko Miyazaki, Masao Ono, Wei Min Qu, Ming Cai Zhang, Shiro Mori, Shuichi Nakatsuru, Yusuke Nakamura, Tatsuya Sawasaki, Yaeta Endo, Masato Nose

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)

Abstract

Potentially, autoimmune diseases develop from a combination of multiple genes with allelic polymorphisms. An MRL/Mp-Faslpr/lpr (MRL/lpr) strain of mice develops autoimmune diseases, including lupus nephritis, but another lpr strain, C3H/HeJ-Faslpr/lpr (C3H/lpr) does not. This indicates that MRL polymorphic genes are involved in the development of the diseases. By quantitative trait loci (QTL) analysis using 527 of the (MRL/lpr × C3H/lpr)F2 mice, we identified a novel locus for susceptibility to lupus nephritis at map position D5Mit115 on chromosome 5, the same alias of the osteopontin (Opn) gene (LOD score = 4.0), susceptible in the MRL allele. In functional analyses of the MRL and C3H Opn alleles using synthetic osteopontin (OPN) made with a new method "cell-free system" with wheat germ ribosomes, the MRL-OPN induced higher expression and production of immunoglobulins as well as cytokines including TNF-α, IL-1β and IFN-γ in splenocytes and/or macrophages than that of the C3H allele. These findings suggest that allelic polymorphism of OPN causes the functional differences in antibody production and macrophage activation between MRL and C3H strains, possibly involved in the development of lupus nephritis.

Original languageEnglish
Pages (from-to)1510-1520
Number of pages11
JournalEuropean Journal of Immunology
Volume35
Issue number5
DOIs
Publication statusPublished - 2005 May 1

Keywords

  • Cell-free protein synthesis
  • Glomerulonephritus
  • Pathogenomics
  • Polymorphic proteins
  • QTL analysis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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