Session Type: ACR Concurrent Abstract Session
Session Time: 9:00AM-10:30AM
Background/Purpose: Cia25/Pia42 is an arthritis severity and joint damage quantitative trait locus on rat chromosome 12 previously identified in an intercross between MHC identical but disease discordant DA (arthritis-susceptible) and ACI (resistant) rats. DA.ACI(Cia25/Pia42) congenic rats were significantly protected in both Pristane and Collagen-induced arthritis (PIA and CIA) compared with DA. This study aimed at positionally identifying the gene accounting for Cia25/Pia42 gene.
Methods: Recombinant subcongenics covering the Cia25/Pia42 interval were generated by backcrossing the original congenic strain with DA using a genotype-guided strategy. Recombinants sharing identical intervals were then intercrossed to homozygozity. PIA was induced in 8-12 week-old subcongenic rats and disease scored for 31 days using a system that correlates with histological damage. Fibroblast-like synoviocytes (FLS) from rats and patients with rheumatoid arthritis (RA) were studied in in vitro invasion assays previously shown to correlate with radiographic damage.
Results: Analyses of 12 different recombinant (R) subcongenic strains reduced the gene-containing interval from 33Mb to a 1.2MB region contained within subcongenic R6. R6 subcongenics had significantly 92% lower median arthritis severity score compared with DA (P<0.001) and were significantly protected from developing cartilage or bone damage (P
Conclusion: Hip1 is a new arthritis severity and joint damage gene that mediates disease at least in part via the regulation of the invasive properties of FLS. The identification of this new gene is the first step towards developing new therapies and a new prognostic biomarker for RA.
To cite this abstract in AMA style:Laragione T, Gulko P, Brenner M. Huntingtin Interacting Protein 1 (Hip1) Is a New Arthritis Severity Gene [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/huntingtin-interacting-protein-1-hip1-is-a-new-arthritis-severity-gene/. Accessed November 29, 2020.
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