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

Genes Immun. 2006 Jul;7(5):335-41. doi: 10.1038/sj.gene.6364304. Epub 2006 May 4.


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< or =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-1beta (IL-1beta) 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Animals
  • Animals, Congenic
  • Arthritis, Experimental / genetics*
  • Arthritis, Experimental / pathology*
  • Arthritis, Rheumatoid / genetics*
  • Autoantibodies / blood
  • Autoantibodies / metabolism
  • Chromosomes, Human, Pair 17*
  • Chromosomes, Mammalian*
  • Disease Models, Animal
  • Genetic Markers
  • Humans
  • Joints / pathology
  • Quantitative Trait, Heritable
  • Rats
  • Rats, Inbred ACI
  • Rats, Inbred Dahl
  • Severity of Illness Index
  • Specific Pathogen-Free Organisms
  • Synteny*


  • Autoantibodies
  • Genetic Markers