title: Modulation of multiple experimental arthritis models by collagen-induced arthritis quantitative trait loci isolated in congenic rat lines: different effects of non-major histocompatibility complex quantitative trait loci in males and females.
abstract: OBJECTIVE
  Collagen-induced arthritis (CIA) is a model of inflammatory arthritis with many similarities to rheumatoid arthritis (RA). We previously mapped in F(2) offspring of CIA-susceptible DA and CIA-resistant F344 rats, 5 quantitative trait loci (QTLs) for which F344 alleles were associated with reduced CIA severity. In the present study, we sought to characterize the independent arthritis-modulating effects of these 5 QTLs.
  
  
  METHODS
  CIA-regulatory regions were transferred from the F344 genome to the DA background or vice versa by repeated backcrossing. The arthritis-modulating effects of the transferred alleles were determined by comparing the severity of experimentally induced arthritis in congenic rats with that in DA rats.
  
  
  RESULTS
  Congenic lines with either the F344 major histocompatibility complex (MHC) on the DA background or the DA MHC on the F344 background were resistant to CIA, confirming both MHC and non-MHC contributions to the genetic regulation of CIA. F344 alleles at the Cia3 and Cia5 regions of chromosomes 4 and 10 reduced CIA severity relative to that observed in DA rats. F344 Cia4 and Cia6 regions of chromosomes 7 and 8 failed to significantly alter CIA severity. Arthritis-modifying effects of Cia4 and Cia6 were, however, detected in pristane-induced and/or Freund's incomplete adjuvant oil-induced arthritis. The arthritis-modifying effects of the non-MHC CIA-regulatory loci differed in males and females.
  
  
  CONCLUSIONS
  These congenic lines confirmed the existence and location of genes that regulate the severity of experimental arthritis in rats. Mechanisms responsible for the sex-specificity of individual arthritis-regulatory loci may explain some of the sex differences observed in RA and other autoimmune diseases in humans.
authors.affiliation: National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland20892, USA. remmerse@mail.nih.gov
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Remmers
authors.forename: Bina
authors.initials: B
authors.lastname: Joe
authors.forename: Marie M
authors.initials: MM
authors.lastname: Griffiths
authors.forename: David E
authors.initials: DE
authors.lastname: Dobbins
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Dracheva
authors.forename: Akira
authors.initials: A
authors.lastname: Hashiramoto
authors.forename: Takefumi
authors.initials: T
authors.lastname: Furuya
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Salstrom
authors.forename: JianPing
authors.initials: J
authors.lastname: Wang
authors.forename: Pércio S
authors.initials: PS
authors.lastname: Gulko
authors.forename: Grant W
authors.initials: GW
authors.lastname: Cannon
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Wilder
mesh_terms: D000818:Animals; D020296:Animals, Congenic / Q000235:genetics* / Q000276:immunology; D016525:Antigenic Modulation / Q000235:genetics* / Q000276:immunology; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D003094:Collagen / Q000276:immunology / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D005620:Freund's Adjuvant / Q000276:immunology / Q000494:pharmacology; D008285:Major Histocompatibility Complex / Q000235:genetics* / Q000276:immunology; D008297:Male; D019655:Quantitative Trait, Heritable; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors; D013729:Terpenes / Q000276:immunology / Q000494:pharmacology; D013997:Time Factors
chemical_list: D013729:Terpenes; C009042:pristane; D003094:Collagen; D005620:Freund's Adjuvant