Open AccessGenetic basis of tissue specificity of vasculitis in MRL/lpr mice
Author(s) -
Yamada Akihiro,
Miyazaki Tatsuhiko,
Lu LingMin,
Ono Masao,
Ito Mitsuko R.,
Terada Miho,
Mori Shiro,
Hata Kazuya,
Nozaki Yoshimi,
Nakatsuru Shuichi,
Nakamura Yusuke,
Onji Morikazu,
Nose Masato
Publication year - 2003
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.10952
Subject(s) - vasculitis , locus (genetics) , pathology , chromosome , biology , genetic linkage , medicine , genetics , gene , disease
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)F 1 , and (MRL/lpr × C3H/lpr)F 2 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 F 2 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 medium‐sized 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.