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Research article - Peer-reviewed, 2000

Genetic control of arthritis in rats

Holmdahl, Rikard; Vingsbo-Lundberg, Carina; Nordquist, Niklas; Olofsson, Peter; Sundvall, Mats; Saxne, Tore; Pettersson, Ulf

Abstract

This study was specifically designed to analyse the genetic control of the chronic disease course for the development of arthritis. Arthritis models with a chronic erosive arthritis are collagen induced arthritis induced with homologous collagen in oil but also arthritis induced with certain non-immunogenic adjuvants such as pristane and avridine. In the presently described experiment we have used pristane induced arthritis. A single injection of 150 mu l pristane induces severe chronic arthritis in DA rats. The disease mimics rheumatoid arthritis in many aspects such as the chronic disease course, an erosive inflammation of peripheral joints, symmetric involvement of the joints and the development of rheumatoid factors. To determine the genetic contribution we have used a number of inbred, recombinant inbred and congenic strains as well as specifically designed segregating crosses. An influence by the MHC region (designated Pia1 locus) on the chronic disease course was determined through the uses of MHC congenic LEW strains in which the RT1-f haplotype conferred highest susceptibility. To map genes outside of MHC we used an F2 cross between the highly susceptible DA and the resistant E3 strains; Loci exclusively associated with different phenotypes of the disease could be identified: Arthritis onset (Pia2 and Pia3). Severity and joint erosions (Pia4). Chronicity (Pia5 and Pia6) and Pial (determined from MHC congenic strains) These findings demonstrates that a chronic self-perpetuative disease, mimicking rheumatoid arthritis, is controlled by different set of genes exclusively linked to different phases of the disease course such as arthritis onset, joint erosions, severity and chronicity.

Keywords

rheumatoid arthritis; pristane induced arthritis; autoimmunity; genetic control; DA rats; E3 rats

Published in

Journal of Experimental Animal Science
2000, Volume: 41, number: 1-2, pages: 7-13
Publisher: GUSTAV FISCHER VERLAG VILLENGANG 2, D-07745 JENA, GERMANY

    UKÄ Subject classification

    Medical Genetics
    Immunology in the medical area

    Publication identifier

    DOI: https://doi.org/10.1016/S0939-8600(00)80018-8

    Permanent link to this page (URI)

    https://res.slu.se/id/publ/38770