DESCRIPTION:

QTL Associated with Joint/bone inflammation. On Chromosome 10 with a LOD score= , p-value =. From a(n) of

LABEL:

QTL-Pia26-Rat-Chr 10

SCORE TYPE:

Binary

DATE ADDED:

2015-06-10

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Brenner M, Meng HC, Yarlett NC, Joe B, Griffiths MM, Remmers EF, Wilder RL, Gulko PS

TITLE:

The non-MHC quantitative trait locus Cia5 contains three major arthritis genes that differentially regulate disease severity, pannus formation, and joint damage in collagen- and pristane-induced arthritis.

JOURNAL:

Journal of immunology (Baltimore, Md. : 1950) None None, Vol 174, pp. 7894-903

ABSTRACT:

1. J Immunol. 2005 Jun 15;174(12):7894-903. The non-MHC quantitative trait locus Cia5 contains three major arthritis genes that differentially regulate disease severity, pannus formation, and joint damage in collagen- and pristane-induced arthritis. Brenner M(1), Meng HC, Yarlett NC, Joe B, Griffiths MM, Remmers EF, Wilder RL, Gulko PS. Author information: (1)Laboratory of Experimental Rheumatology, Robert S. Boas Center for Genomics and Human Genetics and Graduate School of Molecular Medicine, North Shore-Long Island Jewish (LIJ) Research Institute, Manhasset, NY 11030, USA. Cia5 is a locus on rat chromosome 10 which regulates the severity of collagen- and pristane-induced arthritis (CIA and PIA). To refine the region toward positional identification, Cia5 subcongenic strains were generated and studied in PIA and CIA. The protective effect of the telomeric locus Cia5a was confirmed in both models. A second arthritis severity locus (Cia5d) was identified within the most centromeric portion of Cia5. DA.F344(Cia5d) rats had a significantly lower median arthritis severity index in PIA, but not in CIA, compared with DA. On histologic analyses DA.F344(Cia5a) and DA.F344(Cia5d) congenics with PIA preserved a nearly normal joint architecture compared with DA, including significant reduction in synovial hyperplasia, pannus, angiogenesis, inflammatory infiltration, bone and cartilage erosions. Cia5 and Cia5a synovial levels of IL-1beta mRNA were reduced. Although both DA.F344(Cia5) and DA.F344(Cia5a) rats were protected in CIA, the arthritis scores of DA.F344(Cia5) were significantly higher than those of DA.F344(Cia5a), suggesting the existence of a third locus where F344-derived alleles centromeric from Cia5a contribute to increased arthritis severity. The existence of the third locus was further supported by higher levels of autoantibodies against rat type II collagen in DA.F344(Cia5) congenics compared with DA.F344(Cia5a). Our results determined that Cia5 contains three major arthritis severity regulatory loci regulating central events in the pathogenesis of arthritis, and differentially influencing CIA and PIA. These loci are syntenic to regions on human chromosomes 17q and 5q implicated in the susceptibility to rheumatoid arthritis, suggesting that the identification of these genes will be relevant to human disease. PMID: 15944295 [PubMed - indexed for MEDLINE] PUBMED: 15944295
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