Genetic dissection of vasculitis in MRL/lpr lupus mice: a novel susceptibility locus involving the CD72c allele.
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 CD72(b). 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.
Department of Pathology, Ehime University School of Medicine, Japan.
W M
WM
Qu
T
T
Miyazaki
M
M
Terada
L M
LM
Lu
M
M
Nishihara
A
A
Yamada
S
S
Mori
Y
Y
Nakamura
H
H
Ogasawara
C
C
Yazawa
S
S
Nakatsuru
M
M
Nose
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics*; D002874:Chromosome Mapping; D018076:DNA, Complementary; D005260:Female; D020022:Genetic Predisposition to Disease; D015994:Incidence; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012333:RNA, Messenger; D014657:Vasculitis / Q000453:epidemiology / Q000235:genetics*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C064228:CD72 protein, human; D018076:DNA, Complementary; D012333:RNA, Messenger