RGD Reference Report - Complex genetic control in a rat model for rheumatoid arthritis. - Rat Genome Database

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Complex genetic control in a rat model for rheumatoid arthritis.

Authors: Nordquist, N  Olofsson, P  Vingsbo-Lundberg, C  Petterson, U  Holmdahl, R 
Citation: Nordquist N, etal., J Autoimmun 2000 Dec;15(4):425-32.
RGD ID: 629570
Pubmed: PMID:11090241   (View Abstract at PubMed)
DOI: DOI:10.1006/jaut.2000.0450   (Journal Full-text)

We have defined previously five quantitative trait loci controlling development of pristane-induced arthritis in a cross between E3 and DA rats. To define new loci controlling the disease we have mapped three recombinant inbred strains between DA and E3 and analysed an F2 cross between DA rats and one of these RI strains. Two novel loci affecting disease severity are identified on chromosome 1 (Pia8) and chromosome 4 (Pia7) respectively. We could also reproduce the earlier identified Pia3 locus on chromosome 6 associated with arthritis onset. In the original E3xDA F2 cross, neither of the loci Pia7, Pia8, or Pia1 showed any association with arthritis. To investigate the possibility of interacting loci preventing the phenotypic expression of other loci, the E3xDA F2 cross was re-analysed with a model for a two locus interaction, knowing the presence of these newly identified loci. We found suggestive evidence for an interaction where an effect of Pia7 and Pia1 on disease severity depends on DA homozygosity at specific loci, which themselves do not confer susceptibility. This shows that additional disease associated loci can be identified if other loci are neutralized. This will be of importance for understanding the complex genetics controlling rheumatoid arthritis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Arthritis  IAGP 629570 RGD 
Experimental Arthritis  IDA 629570 RGD 
rheumatoid arthritis severityIAGPpristane629570; 629570compared to control strain E3/ZtmRhdRGD 
rheumatoid arthritis MODEL: controlIAGPpristane629570compared to induced strain DA/ZtmRhdRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
arthritis severityIAGPpristane629570compared to control strain E3/ZtmRhdRGD 
decreased susceptibility to induced arthritis resistanceIAGPpristane629570compared to induced strain DA/ZtmRGD 
increased susceptibility to induced arthritis severityIAGPpristane629570; 629570compared to control strain E3/ZtmRhdRGD 
joint swelling  IAGP 629570 RGD 
rheumatoid arthritis severityIAGPpristane629570compared to control strain E3/ZtmRhdRGD 

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Objects Annotated

QTLs
Pia7  (Pristane induced arthritis QTL 7)
Pia8  (Pristane induced arthritis QTL 8)

Objects referenced in this article
QTL Pia9 Pristane induced arthritis QTL 9 Rattus norvegicus

Additional Information