RGD Reference Report - High resolution mapping of an arthritis susceptibility locus on rat chromosome 4, and characterization of regulated phenotypes. - Rat Genome Database

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High resolution mapping of an arthritis susceptibility locus on rat chromosome 4, and characterization of regulated phenotypes.

Authors: Ribbhammar, U  Flornes, L  Backdahl, L  Luthman, H  Fossum, S  Lorentzen, JC 
Citation: Ribbhammar U, etal., Hum Mol Genet 2003 Sep 1;12(17):2087-96.
RGD ID: 730281
Pubmed: PMID:12915467   (View Abstract at PubMed)
DOI: DOI:10.1093/hmg/ddg224   (Journal Full-text)

The rat Natural Killer cell gene Complex (NKC) encodes molecules that can regulate immunity. It is located within an interval on DA rat chromosome 4 (RNO4) that is linked to immune-mediated inflammatory joint diseases, including oil-induced arthritis (OIA). We aimed to test the hypothesis that NKC regulates arthritis, by performing advanced mapping of arthritis and additional phenotypes induced by an intradermal injection of incomplete Freund's adjuvant-oil. Reciprocal transfer of RNO4 intervals established that alleles from DA confer arthritis susceptibility to inbred LEW.1AV1 and PVG.1AV1 rats, whereas LEW.1AV1 and PVG.1AV1 alleles confer resistance to inbred DA. Subcongenic strains with PVG.1AV1 alleles introduced on DA allowed mapping of disease predisposition to 0.8 cM on the cytogenetic band 4q42, within the quantitative trait locus oil-induced arthritis-2 (Oia2), but outside the NKC. Alleles in Oia2 regulated arthritis in an additive fashion, and determined arthritis incidence, severity and day of onset, in both males and females. Besides macroscopic joint-inflammation, Oia2 also regulated other oil-induced phenotypes, including lymphoplasia and plasma levels of the inflammation marker alpha1-acid glycoprotein. The high-impact Oia2 region harbors gene sequences similar to human C3AR1, Ribosomal protein L7, DNAJA2, C-type lectins, C1s and CD163. These candidate disease genes may be of general interest, given that rat 4q42, and the syntenic mouse 6F2 and human 12p13 regions are linked to several inflammatory diseases, including rheumatoid arthritis.



Disease Annotations    Click to see Annotation Detail View
RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
LEW.1AV1/KiniRatarthritis MODEL: controlIAGPFreund's incomplete adjuvantcompared to inducible strain DA/ZtmKiniRGD 
PVG.1AV1/KiniRatarthritis MODEL: controlIAGPFreund's incomplete adjuvantcompared to inducible strain DA/ZtmKiniRGD 
DA/ZtmKiniRatExperimental Arthritis MODEL: inducedIAGPFreund's incomplete adjuvantcompared to control strains PVG.1AV1/Kini, LEW.1AV1/KiniRGD 
Oia7RatExperimental Arthritis  IDA  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
DA/ZtmKiniRatabnormal acute phase protein level severityIAGPFreund's incomplete adjuvantcompared to control strains PVG.1AV1/Kini, LEW.1AV1/KiniRGD 
DA/ZtmKiniRatabnormal liver weight severityIAGPFreund's incomplete adjuvantcompared to control strains PVG.1AV1/Kini, LEW.1AV1/KiniRGD 
DA/ZtmKiniRatabnormal spleen weight severityIAGPFreund's incomplete adjuvantcompared to control strains PVG.1AV1/Kini, LEW.1AV1/KiniRGD 
DA/ZtmKiniRatabnormal thymus weight severityIAGPFreund's incomplete adjuvantcompared to control strains PVG.1AV1/Kini, LEW.1AV1/KiniRGD 
DA/ZtmKiniRatautoimmune arthritis severityIAGPFreund's incomplete adjuvantcompared to control strains PVG.1AV1/Kini, LEW.1AV1/KiniRGD 
DA/ZtmKiniRatenlarged inguinal lymph nodes severityIAGPFreund's incomplete adjuvantcompared to control strains PVG.1AV1/Kini, LEW.1AV1/KiniRGD 
DA/ZtmKiniRatincreased inflammatory response severityIAGPFreund's incomplete adjuvantcompared to control strains PVG.1AV1/Kini, LEW.1AV1/KiniRGD 
DA/ZtmKiniRatjoint swelling severityIAGPFreund's incomplete adjuvantcompared to control strains PVG.1AV1/Kini, LEW.1AV1/KiniRGD 
Oia7Ratjoint swelling  IAGP  RGD 
DA/ZtmKiniRatrheumatoid arthritis severityIAGPFreund's incomplete adjuvantcompared to control strains PVG.1AV1/Kini, LEW.1AV1/KiniRGD 
DA/ZtmKiniRatweight loss severityIAGPFreund's incomplete adjuvantcompared to control strains PVG.1AV1/Kini, LEW.1AV1/KiniRGD 

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Objects Annotated

QTLs
Oia7  (Oil induced arthritis QTL 7)

Objects referenced in this article
Strain DA.LEW.1AV1-(D4Mgh17-D4Mgh21)/Kiru null Rattus norvegicus
Strain DA.PVG.1AV1-(D4Got126-D4Rat203)/Kiru null Rattus norvegicus
Strain DA.PVG.1AV1-(D4Mit22-D4Rat84)/Kiru null Rattus norvegicus
Strain DA.PVG.1AV1-(D4Rat113-D4Rat62)/Kiru null Rattus norvegicus
Strain DA.PVG.1AV1-(D4Rat155-D4Rat113)/Kiru null Rattus norvegicus
Strain DA.PVG.1AV1-(D4Rat203-D4Got130)/Kiru null Rattus norvegicus
Strain DA.PVG.1AV1-(D4Rat203-D4Mit22)/Kiru null Rattus norvegicus
Strain DA.PVG.1AV1-(D4Rat62-D4Got136)/Kiru null Rattus norvegicus
Strain DA.PVG.1AV1-(D4Rat63-D4Rat203)/Kiru null Rattus norvegicus
Strain DA.PVG.1AV1-(D4Rat63-D4Rat84)/Kiru null Rattus norvegicus
Strain LEW.1AV1 null Rattus norvegicus
Strain LEW.1AV1.DA-(D4Mgh17-D4Rat203)/Kiru null Rattus norvegicus
Strain PVG.1AV1.DA-(D4Mgh17-D4Rat84)/Kiru null Rattus norvegicus

Additional Information