Genetic basis of tissue specificity of vasculitis in MRL/lpr mice.
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 x C3H/lpr)F(1), and (MRL/lpr x 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.


CONCLUSIONS
Systemic vasculitis in MRL/lpr mice is genetically controlled with cumulative effects of multiple gene loci, each of which has tissue specificity.
Yamada
Akihiro
A
Ehime University School of Medicine, Ehime, Japan.
Miyazaki
Tatsuhiko
T
Lu
Ling-Min
LM
Ono
Masao
M
Ito
Mitsuko R
MR
Terada
Miho
M
Mori
Shiro
S
Hata
Kazuya
K
Nozaki
Yoshimi
Y
Nakatsuru
Shuichi
S
Nakamura
Yusuke
Y
Onji
Morikazu
M
Nose
Masato
M
D000818:Animals; D001011:Aorta / Q000473:pathology; D003433:Crosses, Genetic; D004247:DNA / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D008126:Lod Score; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H / Q000235:genetics; D019463:Mice, Inbred MRL lpr / Q000235:genetics*; D018895:Microsatellite Repeats; D009928:Organ Specificity / Q000235:genetics*; D016133:Polymerase Chain Reaction; D040641:Quantitative Trait Loci; D014657:Vasculitis / Q000235:genetics* / Q000473:pathology
D004247:DNA