Genetic basis of tissue specificity of vasculitis in MRL/lpr mice

Akihiro Yamada, Tatsuhiko Miyazaki, Ling Min Lu, Masao Ono, Mitsuko R. Ito, Miho Terada, Shiro Mori, Kazuya Hata, Yoshimi Nozaki, Shuichi Nakatsuru, Yusuke Nakamura, Morikazu Onji, Masato Nose

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18 Citations (Scopus)

Abstract

Objective. To clarify the mode of inheritance of the tissue distribution of vasculitis in MRL/Mp.lpr/lpr (MRL/lpr) lupus-prone mice and to identify the susceptibility loci. Methods. Vasculitis in individual MRL/lpr, C3H/ HeJ-lpr/lpr (C3H/lpr), (MRL/lpr × C3H/lpr)F1, and (MRL/lpr × C3H/lpr)F2 intercross mice was analyzed by histopathologic grading of main branches of the aorta and of medium-sized arteries in the lower limbs. Genomic DNA samples from F2 intercross mice were examined by simple sequence-length polymorphism analysis, and the polymorphic microsatellite markers highly associated with vasculitis in each tissue were determined as vasculitis susceptibility loci. Results. A susceptibility locus with significant linkage to vasculitis of main branches of the aorta was mapped on chromosome 4 at D4Mit213 (map position 13.3cM) selectively in males, while vasculitis of mediumsized arteries in the lower limbs was mapped to different chromosomes: at D8Mit31 on chromosome 8 (map position 33.0) selectively in females and at D5Mit36 on chromosome 5 (map position 65.0). All of these were different from the previously defined loci governing susceptibility to vasculitis involving the kidneys. Conclusion. Systemic vasculitis in MRL/lpr mice is genetically controlled with cumulative effects of multiple gene loci, each of which has tissue specificity.

Original languageEnglish
Pages (from-to)1445-1451
Number of pages7
JournalArthritis and Rheumatism
Volume48
Issue number5
DOIs
Publication statusPublished - 2003 May 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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    Yamada, A., Miyazaki, T., Lu, L. M., Ono, M., Ito, M. R., Terada, M., Mori, S., Hata, K., Nozaki, Y., Nakatsuru, S., Nakamura, Y., Onji, M., & Nose, M. (2003). Genetic basis of tissue specificity of vasculitis in MRL/lpr mice. Arthritis and Rheumatism, 48(5), 1445-1451. https://doi.org/10.1002/art.10952