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: (View Article at PubMed) PMID:10857786
DOI: Full-text: DOI:10.1002/1529-0131(200006)43:6<1278::AID-ANR10>3.0.CO;2-S

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.

Annotation

Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype
Phenotype Values via PhenoMiner

View PhenoMiner data from this reference here 

Objects Annotated

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

QTLs
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)

Strains
DA/Bkl  (NA)

Objects referenced in this article
0 D12Wox10 D12Wox10 All species
0 D20Arb2 D20Arb2 All species
0 D3Wox9 D3Wox9 All species
0 D20Wox3 D20Wox3 All species
0 D4Mit14 D4Mit14 All species
0 D3Mit9 D3Mit9 All species
0 D19Mit8 D19Mit8 All species
0 D4Mit17 D4Mit17 All species
0 D19Mit5 D19Mit5 All species
0 D3Mgh5 D3Mgh5 All species
0 D4Mgh11 D4Mgh11 All species
0 D9Rat44 D9Rat44 All species
0 D12Arb6 D12Arb6 All species
0 D9Wox19 D9Wox19 All species
0 D12Wox5 D12Wox5 All species
0 D19Arb7 D19Arb7 All species
0 D20Arb8 D20Arb8 All species
0 BBDR/Rhw null All species
0 BN BN All species
0 BN/SsN null All species
0 C3 complement C3 All species
0 C5 complement C5 All species
0 Cia1 Collagen induced arthritis QTL 1 All species
0 Cia15 Collagen induced arthritis QTL 15 All species
0 DA DA All species
0 F344/NRrrc null All species
0 Flt1 Fms related receptor tyrosine kinase 1 All species
0 Gpd2 glycerol-3-phosphate dehydrogenase 2 All species
0 Hspb1 heat shock protein family B (small) member 1 All species
0 Ncf1 neutrophil cytosolic factor 1 All species
0 Pdgfa platelet derived growth factor subunit A All species
0 Ptgs1 prostaglandin-endoperoxide synthase 1 All species
0 Scn2a sodium voltage-gated channel alpha subunit 2 All species
0 Vav1 vav guanine nucleotide exchange factor 1 All species

Additional Information