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Localization of genetic loci controlling antibody response to autologous collagen in rats with collagen-induced arthritis (CIA)

Authors: Longman, RE  Remmers, EF  Cannon, GW  Griffiths, MM  Wilder, RL 
Citation: Longman RE, Remmers EF, Cannon GW, Griffiths MM, Wilder RL. 1996 Arthritis Rheum. 39(Suppl 9):S117

Following immunization with type II bovine collagen, susceptible rat strains mount an autoimmune response to rat collagen and develop an inflammatory arthritis resembling rheumatoid arthritis. To define the relationship between collagen autoantibody production and arthritis, we measured anti-rat type II collagen IgG levels in serum from rats immunized with bovine collagen. CIA-resistant F344 cats produced 7,000 + 7,700 units/ml (mean + SD). CIA-susceptible DA rats produced 25,000 +17,000 units/ml. F1 hybrids which develop arthritis, but of reduced severity compared to the DA parental strains, produced 70,000 +35,000 units/ml (F344, DA, and F1 antibody production are significantly different from each other, p < 0.0001). Intercross progeny of the two strains, consisting of 502 animals, exhibited a wide range of antibody levels (range = 280 to 210,000 units/ml , median = 27,000 units/ml). The antibody levels of the F2 animals did not correlate with disease severity (r = 0.029). However, disease incidence was associated with a threshold level of 1,400 units/ml. We analyzed genetic control of the autoantibody response in the F2 population as a quantitative trait. We found significant evidence for a quantitative trait locus (QTL) on chromosome 20 linked to the rat MHC (p < 1.9E-17). A non-MHC-linked locus on chromosome 10, differing from the arthritis severity locus cia5, also demonstrated significant linkage (p<2.5E-5). High antibody production was associated with at least one DA allele at the MHC-linked locus and F344 homozygosity at the chromosome 10 locus. Genetic mapping of loci that control collagen autoantibody production is the first step in identifying the genes that control this complex phenotype and determining the relationship with arthritis.


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CRRD Object Information
CRRD ID: 61518
Created: 2001-03-13
Species: All species
Last Modified: 2001-03-14
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.