RGD Reference Report - Identification of four new quantitative trait loci regulating arthritis severity and one new quantitative trait locus regulating autoantibody production in rats with collagen-induced arthritis. - Rat Genome Database

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Identification of four new quantitative trait loci regulating arthritis severity and one new quantitative trait locus regulating autoantibody production in rats with collagen-induced arthritis.

Authors: Griffiths, MM  Wang, J  Joe, B  Dracheva, S  Kawahito, Y  Shepard, JS  Reese, VR  McCall-Vining, S  Hashiramoto, A  Cannon, GW  Remmers, EF  Wilder, RL 
Citation: Griffiths MM, etal., Arthritis Rheum 2000 Jun;43(6):1278-89
RGD ID: 61066
Pubmed: PMID:10857786   (View Abstract at PubMed)
DOI: DOI:10.1002/1529-0131(200006)43:6<1278::AID-ANR10>3.0.CO;2-S   (Journal Full-text)

OBJECTIVE: Collagen-induced arthritis (CIA) is a polygenic model of experimentally induced autoimmunity and chronic joint inflammation. This study maps genetic loci that regulate CIA susceptibility in DA/Bkl (DA) and BN/SsNHsd (BN) rats. METHODS: Genome scans covering chromosomes 1-20 and interval mapping techniques using 159 simple sequence-length polymorphism markers were used to identify quantitative trait loci (QTLs) that regulate CIA in (DA x BN)F2 hybrids. Serum antibody titers to type II collagen were determined by enzyme-linked immunosorbent assay. RESULTS: DA rats were high responders to porcine type II collagen (PII) and developed severe CIA (100%). BN rats were low responders to PII and resistant to CIA (0%). BN genes strongly repressed PII-induced CIA. Only 12% of (DA x BN)F1 rats (7 of 60) and 31% of (DA x BN)F2 rats (307 of 1,004) developed CIA. Three new QTLs (Cia11, Cia12, and Cia13) with significant logarithm of odds (LOD) scores of 5.6, 4.6, and 4.5, respectively, plus a suggestive QTL (Cia14*, LOD 3.0) regulating arthritis severity were identified on chromosomes 3, 12, 4, and 19. A new QTL, Ciaa3, associating with anticollagen antibody titer (antibody to PII LOD 6.5; antibody to rat type II collagen LOD 5.2) mapped to chromosome 9. Of 10 CIA QTLs previously identified in (DA x F344) and (DA x ACI) rats, only Cia1 in the major histocompatibility complex and a region coincident to Cia5 on chromosome 10 (LOD >8.0) influenced CIA severity in (DA x BN)F2 rats. CONCLUSION: Since CIA exhibits many of the pathologic features of rheumatoid arthritis, the data indicate that the variety of genetic elements regulating human autoimmune and rheumatic diseases may be much larger and more varied than originally envisioned.

RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cia11RatExperimental Arthritis  IDA  RGD 
Cia12RatExperimental Arthritis  IDA  RGD 
Cia14RatExperimental Arthritis  IDA  RGD 
Cia24RatExperimental Arthritis  IDA  RGD 
Ciaa1RatExperimental Arthritis  IDA  RGD 
Ciaa2RatExperimental Arthritis  IDA  RGD 
Ciaa3RatExperimental Arthritis  IDA  RGD 
Flt3RatExperimental Arthritis  IAGP  RGD 
DA/BklRatrheumatoid arthritis inducedIAGPtype II collagencompared to BNRGD 
DA/BklRatrheumatoid arthritis sexual_dimorphism IAGP more severe in female DA/BklRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ciaa3Ratincreased IgG level  QTM  RGD 
DA/BklRatincreased susceptibility to induced arthritis inducedIAGPtype II collagencompared to BN/SsNRGD 
Ciaa1Ratjoint inflammation  QTM  RGD 
Ciaa2Ratjoint inflammation  QTM  RGD 
Ciaa3Ratjoint inflammation  QTM  RGD 
Cia11Ratjoint swelling  QTM  RGD 
Cia12Ratjoint swelling  QTM  RGD 
Cia14Ratjoint swelling  QTM  RGD 
Cia24Ratjoint swelling  QTM  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Flt3  (Fms related receptor tyrosine kinase 3)

Cia11  (Collagen induced arthritis QTL 11)
Cia12  (Collagen induced arthritis QTL 12)
Cia13  (Collagen induced arthritis QTL 13)
Cia14  (Collagen induced arthritis QTL 14)
Cia24  (Collagen induced arthritis QTL 24)
Ciaa1  (CIA Autoantibody QTL 1)
Ciaa2  (CIA Autoantibody QTL 2)
Ciaa3  (CIA Autoantibody QTL 3)

BBDR/Rhw  (NA)
BN  (BN)
BN/SsN  (NA)
DA  (DA)
DA/Bkl  (NA)
F344/NRrrc  (NA)

Objects referenced in this article
Marker D12Wox10 D12Wox10 Rattus norvegicus
Marker D20Arb2 D20Arb2 Rattus norvegicus
Marker D3Wox9 D3Wox9 Rattus norvegicus
Marker D20Wox3 D20Wox3 Rattus norvegicus
Marker D4Mit14 D4Mit14 Rattus norvegicus
Marker D3Mit9 D3Mit9 Rattus norvegicus
Marker D19Mit8 D19Mit8 Rattus norvegicus
Marker D4Mit17 D4Mit17 Rattus norvegicus
Marker D19Mit5 D19Mit5 Rattus norvegicus
Marker D3Mgh5 D3Mgh5 Rattus norvegicus
Marker D4Mgh11 D4Mgh11 Rattus norvegicus
Marker D9Rat44 D9Rat44 Rattus norvegicus
Marker D12Arb6 D12Arb6 Rattus norvegicus
Marker D9Wox19 D9Wox19 Rattus norvegicus
Marker D12Wox5 D12Wox5 Rattus norvegicus
Marker D19Arb7 D19Arb7 Rattus norvegicus
Marker D20Arb8 D20Arb8 Rattus norvegicus
QTL Aia1 Adjuvant induced arthritis QTL 1 Rattus norvegicus
Gene C3 complement C3 Rattus norvegicus
Gene C5 complement C5 Rattus norvegicus
QTL Cia1 Collagen induced arthritis QTL 1 Rattus norvegicus
QTL Cia15 Collagen induced arthritis QTL 15 Rattus norvegicus
Gene Flt1 Fms related receptor tyrosine kinase 1 Rattus norvegicus
Gene Gpd2 glycerol-3-phosphate dehydrogenase 2 Rattus norvegicus
Gene Hspb1 heat shock protein family B (small) member 1 Rattus norvegicus
Gene Ncf1 neutrophil cytosolic factor 1 Rattus norvegicus
Gene Pdgfa platelet derived growth factor subunit A Rattus norvegicus
Gene Ptgs1 prostaglandin-endoperoxide synthase 1 Rattus norvegicus
Gene Scn2a sodium voltage-gated channel alpha subunit 2 Rattus norvegicus
Gene Vav1 vav guanine nucleotide exchange factor 1 Rattus norvegicus

Additional Information