RGD Reference Report - Identification and isolation of dominant susceptibility loci for pristane-induced arthritis. - Rat Genome Database

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Identification and isolation of dominant susceptibility loci for pristane-induced arthritis.

Authors: Olofsson, P  Holmberg, J  Pettersson, U  Holmdahl, R 
Citation: Olofsson P, etal., J Immunol 2003 Jul 1;171(1):407-16.
RGD ID: 631850
Pubmed: (View Article at PubMed) PMID:12817024

Rheumatoid arthritis is a chronic inflammatory autoimmune disorder, controlled by multiple genes as well as environmental factors. With animal models, like the pristane-induced arthritis (PIA) in rats, it is possible to reduce the environmental effects and the genetic heterogeneity to identify chromosomal regions harboring genes responsible for the arthritis development. The PIA model has proved to be useful for identifying gene regions controlling different phases of the disease based on intercrosses between the resistant E3 and the susceptible DA rat. We have now performed a high-powered backcross analysis that confirms previous intercross-based data but also identifies additional loci. Earlier identified PIA loci were reproduced with high significance; Pia1 (MHC region on chromosome 20), Pia4 (chromosome 12), and Pia7 (chromosome 4) are all major regulators of PIA severity and were also found to operate in concert. These three loci were verified in congenic strains using both disease- and arthritis-inflammatory-related subphenotypes as traits. We were also able to detect five new quantitative trait loci with dominant effects on PIA: Pia10, Pia12, Pia13, Pia14, and Pia15 on chromosomes 10, 6, 7, 8, and 18, respectively. These data highlight the usefulness of the statistical power obtained in a backcross of a complex disease like arthritis.



Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype

Objects Annotated

QTLs
Pia15  (Pristane induced arthritis QTL 15)
Pia16  (Pristane induced arthritis QTL 16)
Pia17  (Pristane induced arthritis QTL 17)
Pia18  (Pristane induced arthritis QTL 18)
Pia19  (Pristane induced arthritis QTL 19)
Pia21  (Pristane induced arthritis QTL 21)
Pia22  (Pristane induced arthritis QTL 22)
Pia23  (Pristane induced arthritis QTL 23)

Objects referenced in this article
Strain DA/ZtmRhd null Rattus norvegicus
Strain E3/ZtmRhd null Rattus norvegicus

Additional Information