RGD Reference Report - Genetic dissection of a rat model for rheumatoid arthritis: significant gender influences on autosomal modifier loci - Rat Genome Database

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Genetic dissection of a rat model for rheumatoid arthritis: significant gender influences on autosomal modifier loci

Authors: Furuya, T  Salstrom, JL  McCall-Vining, S  Cannon, GW  Joe, B  Remmers, EF  Griffiths, MM  Wilder, RL 
Citation: Furuya T, etal., Hum Mol Genet 2000 Sep 22;9(15):2241-50
RGD ID: 61067
Web Url: http://hmg.oupjournals.org/cgi/content/abstract/9/15/2241
Pubmed: PMID:11001927   (View Abstract at PubMed)

Rheumatoid arthritis (RA) is a common, chronic, autoimmune, inflammatory disease that is influenced by genetic factors including gender. Many studies suggest that the genetic risk for RA is determined by the MHC, in particular class II alleles with a 'shared epitope' (SE), and multiple non-MHC loci. Other studies indicate that RA and other autoimmune diseases, in particular insulin-dependent diabetes mellitus (IDDM) and autoimmune thyroid disease (ATD), share genetic risk factors. Rat collagen-induced arthritis (CIA) is an experimental model with many features that resemble RA. The spontaneous diabetes-resistant bio-breeding rat, BB(DR), is of interest because it is susceptible to experimentally induced CIA, IDDM and ATD, and it has an SE in its MHC class II allele. To explore the genetics of CIA, including potential gender influences and the genetic relationships between CIA and other autoimmune diseases, we conducted a genome-wide scan for CIA regulatory loci in the F(2) progeny of BB(DR) and CIA-resistant BN rats. We identified 10 quantitative trait loci (QTLs), including 5 new ones (Cia15, Cia16*, Cia17, Cia18* and Cia19 on chromosomes 9, 10, 18 and two on the X chromosome, respectively), that regulated CIA severity. We also identified four QTLs, including two new ones (Ciaa4* and Ciaa5* on chromosomes 4 and 5, respectively), that regulated autoantibody titer to rat type II collagen. Many of these loci appeared to be gender influenced, and most co-localized with several other autoimmune trait loci. Our data support the view that multiple autoimmune diseases may share genetic risk factors, and suggest that many of these loci are gender influenced.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cia13RatExperimental Arthritis  IDA  RGD 
Cia15RatExperimental Arthritis  IDA  RGD 
Cia16RatExperimental Arthritis  IDA  RGD 
Cia17RatExperimental Arthritis  IDA  RGD 
Cia18RatExperimental Arthritis  IDA  RGD 
Cia19RatExperimental Arthritis  IDA  RGD 
Cia6RatExperimental Arthritis  IDA  RGD 
Cia7RatExperimental Arthritis  IDA  RGD 
Ciaa4RatExperimental Arthritis  IDA  RGD 
Ciaa5RatExperimental Arthritis  IDA  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ciaa4Ratincreased IgG level  QTM  RGD 
Ciaa5Ratincreased IgG level  QTM  RGD 
BBDR/RhwRatincreased inflammatory response inducedIAGPtype II collagencompared to BNRGD 
Cia13Ratjoint inflammation  QTM  RGD 
Cia13Ratjoint swelling  QTM  RGD 
Cia15Ratjoint swelling  QTM  RGD 
Cia16Ratjoint swelling  QTM  RGD 
Cia17Ratjoint swelling  QTM  RGD 
Cia18Ratjoint swelling  QTM  RGD 
Cia19Ratjoint swelling  QTM  RGD 
Cia6Ratjoint swelling  QTM  RGD 
Cia7Ratjoint swelling  QTM  RGD 

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Objects Annotated

QTLs
Cia1  (Collagen induced arthritis QTL 1)
Cia13  (Collagen induced arthritis QTL 13)
Cia15  (Collagen induced arthritis QTL 15)
Cia16  (Collagen induced arthritis QTL 16)
Cia17  (Collagen induced arthritis QTL 17)
Cia18  (Collagen induced arthritis QTL 18)
Cia19  (Collagen induced arthritis QTL 19)
Cia2  (Collagen induced arthritis QTL 2)
Cia5  (Collagen induced arthritis QTL 5)
Cia6  (Collagen induced arthritis QTL 6)
Cia7  (Collagen induced arthritis QTL 7)
Ciaa1  (CIA Autoantibody QTL 1)
Ciaa4  (CIA Autoantibody QTL 4)
Ciaa5  (CIA Autoantibody QTL 5)

Strains
BBDR/Rhw  (NA)
BN  (BN)
DA  (DA)
DA/Bkl  (NA)
F344/NHsd  (F344/NHsd)

Objects referenced in this article
Marker D18Mit5 D18Mit5 Rattus norvegicus
Marker D2Mit24 D2Mit24 Rattus norvegicus
Marker D20Arb2 D20Arb2 Rattus norvegicus
Marker D20Wox3 D20Wox3 Rattus norvegicus
Marker D2Mit17 D2Mit17 Rattus norvegicus
Marker D4Mit14 D4Mit14 Rattus norvegicus
Marker D2Mit23 D2Mit23 Rattus norvegicus
Marker D4Mit17 D4Mit17 Rattus norvegicus
Marker D8Mgh11 D8Mgh11 Rattus norvegicus
Marker DXMgh9 DXMgh9 Rattus norvegicus
Marker D5Mgh13 D5Mgh13 Rattus norvegicus
Marker D4Mgh18 D4Mgh18 Rattus norvegicus
Marker D9Mgh5 D9Mgh5 Rattus norvegicus
Marker D8Mgh4 D8Mgh4 Rattus norvegicus
Marker D4Mgh11 D4Mgh11 Rattus norvegicus
Marker D5Mgh8 D5Mgh8 Rattus norvegicus
Marker DXRat66 DXRat66 Rattus norvegicus
Marker D10Rat11 D10Rat11 Rattus norvegicus
Marker D10Rat49 D10Rat49 Rattus norvegicus
Marker D9Rat44 D9Rat44 Rattus norvegicus
Marker D10Rat95 D10Rat95 Rattus norvegicus
Marker D8Rat71 D8Rat71 Rattus norvegicus
Marker D18Rat82 D18Rat82 Rattus norvegicus
Marker D9Arb7 D9Arb7 Rattus norvegicus
Marker D5Wox3 D5Wox3 Rattus norvegicus
Marker DXWox3 DXWox3 Rattus norvegicus
Marker D9Wox19 D9Wox19 Rattus norvegicus
Marker DXWox2 DXWox2 Rattus norvegicus
Marker D20Arb8 D20Arb8 Rattus norvegicus
Gene C3 complement C3 Rattus norvegicus
Gene Cd4 Cd4 molecule Rattus norvegicus
Gene Cd69 Cd69 molecule Rattus norvegicus
QTL Cia4 Collagen induced arthritis QTL 4 Rattus norvegicus
QTL Ciaa3 CIA Autoantibody QTL 3 Rattus norvegicus
Strain F344/NRrrc null Rattus norvegicus
Gene Jun Jun proto-oncogene, AP-1 transcription factor subunit Rattus norvegicus
QTL Oia2 Oil induced arthritis QTL 2 Rattus norvegicus
QTL Pia7 Pristane induced arthritis QTL 7 Rattus norvegicus
Gene Tnfrsf1a TNF receptor superfamily member 1A Rattus norvegicus
Gene Vav1 vav guanine nucleotide exchange factor 1 Rattus norvegicus

Additional Information