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- Title
Cia27 is a novel non-MHC arthritis severity locus on rat chromosome 10 syntenic to the rheumatoid arthritis 17q22–q25 locus.
- Authors
Brenner, M; Laragione, T; Yarlett, N C; Li, W; Mello, A; Gulko, P S
- Abstract
Cia27 on rat chromosome 10 is a collagen-induced arthritis (CIA) severity quantitative trait locus originally identified in a study of (DA × 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 (P0.001). 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-1β (IL-1β) 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.Genes and Immunity (2006) 7, 335–341. doi:10.1038/sj.gene.6364304; published online 4 May 2006
- Subjects
CHROMOSOMES; LABORATORY rats; ARTHRITIS; MESSENGER RNA; INTERLEUKIN-1
- Publication
Genes & Immunity, 2006, Vol 7, Issue 5, p335
- ISSN
1466-4879
- Publication type
Article
- DOI
10.1038/sj.gene.6364304