1. Arthritis Rheum. 2000 Jun;43(6):1278-89.
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.
Griffiths MM(1), Wang J, Joe B, Dracheva S, Kawahito Y, Shepard JS, Reese VR,
McCall-Vining S, Hashiramoto A, Cannon GW, Remmers EF, Wilder RL.
Author information:
(1)Department of Veterans Affairs Medical Center, and University of Utah, Salt
Lake City, USA.
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.
PMID: 10857786 [PubMed - indexed for MEDLINE]
PUBMED: 10857786
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