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: PMID:12817024   (View Abstract at PubMed)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Pia15RatExperimental Arthritis  IDA  RGD 
Pia16RatExperimental Arthritis  IDA  RGD 
Pia17RatExperimental Arthritis  IDA  RGD 
Pia18RatExperimental Arthritis  IDA  RGD 
Pia19RatExperimental Arthritis  IDA  RGD 
Pia21RatExperimental Arthritis  IDA  RGD 
Pia22RatExperimental Arthritis  IAGP  RGD 
Pia23RatExperimental Arthritis  IDA  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
DA.E3-(D20Wox3-D20Mgh4)/RhdRatdecreased double-positive T cell number severityIAGPpristanecompared to inducible strain DA/ZtmRhdRGD 
DA.E3-(D12Got46-D12Rat26)/RhdRatdecreased susceptibility to induced arthritis severityIAGPpristanecompared to inducible strain DA/ZtmRhdRGD 
DA.E3-(D4Mit16-D4Mgh11)/RhdRatdecreased susceptibility to induced arthritis inducedIAGPpristanecompared to treated DA/ZtmRhdRGD 
DA.E3-(D4Mit16-D4Mgh11)/RhdRatdecreased susceptibility to induced arthritis severityIAGPpristanecompared to inducible strain DA/ZtmRhdRGD 
Pia21Ratdecreased susceptibility to induced joint inflammation  IDA  RGD 
Pia15Ratjoint swelling  QTM  RGD 
Pia16Ratjoint swelling  QTM  RGD 
Pia17Ratjoint swelling  QTM  RGD 
Pia18Ratjoint swelling  QTM  RGD 
Pia19Ratjoint swelling  QTM  RGD 
Pia23Ratjoint swelling  IAGP  RGD 

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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)


Additional Information