Genetic dissection of vasculitis in MRL/lpr lupus mice: A novel susceptibility locus involving the CD72(c) allele

Wei Min Qu, Tatsuhiko Miyazaki, Miho Terada, Ling Min Lu, Miyuki Nishihara, Akihiro Yamada, Shiro Mori, Yusuke Nakamura, Hideaki Ogasawara, Chie Yazawa, Syuichi Nakatsuru, Masato Nose

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

Abstract

An MRL/MpJ strain of mice bearing the Fas deletion mutant gene, lpr (MRL/lpr), composed of genomes derived from LG/J, AKR/J, C3H/Di and C57BL/6J mice, develops systemic vasculitis coincidentally with other collagen diseases, but a C3H/HeJ-lpr/lpr (C3H/lpr) strain does not. In a genome-wide screening of the MRL background genes mediating susceptibility to collagen diseases using N2 progeny mice MRL/lpr x (MRL/lpr x C3H/lpr)F1, we previously found that each collagen disease is controlled by a different set of genes. To clarify the candidate genes for vasculitis, we extended the linkage analysis of renal vasculitis to a larger number of N2 mice and to F2 intercross mice. Two distinct recessive susceptibility loci for vasculitis were mapped on chromosome (Chr) 4 at D4Mit89 and D4Mit147 in both progenies. The former was a novel locus for lupus phenotypes, which involved the MRL allele CD72(c) in contrast to the C3H allele CD72b. The one on Chr 3 was a recessive locus which had an inhibitory effect on vasculitis. From their composition these loci seemed to be derived from AKR/J (for one) and LG/J (for another two) strains, and appeared to act in an additive manner on the development of vasculitis, indicating that vasculitis in MRL/lpr mice is inherited in a polygenic manner.

Original languageEnglish
Pages (from-to)2027-2037
Number of pages11
JournalEuropean Journal of Immunology
Volume30
Issue number7
DOIs
Publication statusPublished - 2000

Keywords

  • Genetics
  • MRL mouse
  • Vasculitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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