Cia27 is a novel non-MHC arthritis severity locus on rat chromosome 10 syntenic to the rheumatoid arthritis 17q22-q25 locus.
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.
Brenner
M
M
Laboratory of Experimental Rheumatology, The Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institute for Medical Research at North Shore-LIJ, Manhasset, NY 11030, USA.
Laragione
T
T
Yarlett
N C
NC
Li
W
W
Mello
A
A
Gulko
P S
PS
D000483:Alleles; D000818:Animals; D020296:Animals, Congenic; D001169:Arthritis, Experimental / Q000235:genetics* / Q000473:pathology*; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D001323:Autoantibodies / Q000097:blood / Q000378:metabolism; D002886:Chromosomes, Human, Pair 17; D033481:Chromosomes, Mammalian; D004195:Disease Models, Animal; D005819:Genetic Markers; D006801:Humans; D007596:Joints / Q000473:pathology; D019655:Quantitative Trait, Heritable; D051381:Rats; D011912:Rats, Inbred ACI; D020303:Rats, Inbred Dahl; D012720:Severity of Illness Index; D013047:Specific Pathogen-Free Organisms; D026801:Synteny
D001323:Autoantibodies; D005819:Genetic Markers