Cia27 is a novel non-MHC arthritis severity locus on rat chromosome 10 syntenic to the rheumatoid arthritis 17q22-q25 locus

被引：7

作者：

Brenner, M. ^{[1
]}

Laragione, T. ^{[1
]}

Yarlett, N. C. ^{[1
]}

Li, W. ^{[1
]}

Mello, A. ^{[1
]}

Gulko, P. S. ^{[1
]}

机构：

[1] N Shore LIJ, Feinstein Inst Med Res, Lab Expt Rheumatol, Robert S Boas Ctr Genom & Human Genet, Manhasset, NY 11030 USA

来源：

GENES AND IMMUNITY | 2006年 / 7卷 / 05期

关键词：

autoimmunity; inflammation; genetic; quantitative trait;

D O I：

10.1038/sj.gene.6364304

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Cia27 on rat chromosome 10 is a collagen-induced arthritis (CIA) severity quantitative trait locus originally identified in a study of (DA x ACI) F2. As an initial step towards the positional cloning of the Cia27 gene, a 17 cM (21 Mb)interval from the DA strain (arthritis-susceptible) containing the two- logarithm of odds support interval comprising Cia27 was introgressed into the ACI (arthritis-resistant) background through genotype-guided congenic breeding. ACI. DA(Cia27) congenics developed a significantly more severe form of arthritis (CIA), with a 5.9-fold increase in median arthritis severity index, a parameter known to correlate with synovial inflammation, and cartilage and bone erosions, compared with ACI (P <= 0.001). The arthritis severity enhancing effect could be detected from day 21 onwards. Rats heterozygous at the congenic interval developed a disease similar to ACI rats, suggesting that DA alleles operate in a recessive manner. Levels of autoantibodies anti-rat type II collagen did not correlate with arthritis severity. Synovial tissue mRNA levels of interleukin-1 ss (IL-1 ss) were significantly increased in ACI. DA(Cia27) congenics compared with ACI. These results demonstrate that Cia27 harbors a novel arthritis severity regulatory gene. The identification of this gene should facilitate the identification of the rheumatoid arthritis gene mapped to the human syntenic region on chromosome 17q22-q25.

引用

页码：335 / 341

页数：7

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