Immunogenetics

, Volume 51, Issue 11, pp 930–944

Genetic dissection of collagen-induced arthritis in Chromosome 10 quantitative trait locus speed congenic rats: evidence for more than one regulatory locus and sex influences

  • Bina Joe
  • Elaine F. Remmers
  • David E. Dobbins
  • Jennifer L. Salstrom
  • Takefumi Furuya
  • Svetlana Dracheva
  • Pércio S. Gulko
  • Grant W. Cannon
  • Marie M. Griffiths
  • Ronald L. Wilder
Original Paper

DOI: 10.1007/s002510000231

Cite this article as:
Joe, B., Remmers, E., Dobbins, D. et al. Immunogenetics (2000) 51: 930. doi:10.1007/s002510000231

Abstract.

Rat Chromosome 10 (RNO10) harbors Cia5, a non-MHC quantitative trait locus (QTL) that regulates the severity of type II collagen-induced arthritis (CIA) in DA×F344 and DA×BN F2 rats. CIA is an animal model with many features that resemble rheumatoid arthritis. To facilitate analysis of Cia5 independently of the other CIA regulatory loci on other chromosomes, DA recombinant QTL speed congenic rats, DA.F344(Cia5), were generated. These QTL congenic rats have a large chromosomal segment containing Cia5 (interval size ≤80.1 cM) from CIA-resistant F344 rats introgressed into their genome. Phenotypic analyses of these rats for susceptibility and severity of CIA confirmed that Cia5 is an important disease-modifying locus. CIA severity was significantly lower in the Cia5 congenic rats than in DA controls. We also generated DA Cia5 speed sub-congenic rats, DA.F344(Cia5a), which had a smaller segment of the F344 genome, Cia5a, comprising only the distal q-telomeric end (interval size ≤22.5 cM) of Cia5, introgressed into their genome. DA.F344(Cia5a) sub-congenic rats also exhibited reduced CIA disease severity compared with the parental DA rats. The regulatory effects in both congenic strains were sex influenced. The disease-ameliorating effect of the larger fragment, Cia5, was greater in males than in females, but the effect of the smaller fragment, Cia5a, was greater in females. We also present an improved genetic linkage map covering the Cia5/Cia5a region, which we have integrated with two rat radiation hybrid maps. Comparative homology analysis of this genomic region with mouse and human chromosomes was also undertaken. Regulatory loci for multiple autoimmune/inflammatory diseases in rats (RNO10), mice (MMU11), and humans (HSA17 and HSA5q23–q31) map to chromosomal segments homologous to Cia5 and Cia5a.

Autoimmunity Rheumatoid arthritis Inbred DA rats Inbred F344 rats Genetic maps 

Copyright information

© Springer-Verlag 2000

Authors and Affiliations

  • Bina Joe
    • 1
  • Elaine F. Remmers
    • 1
  • David E. Dobbins
    • 2
  • Jennifer L. Salstrom
    • 1
  • Takefumi Furuya
    • 1
  • Svetlana Dracheva
    • 1
  • Pércio S. Gulko
    • 3
  • Grant W. Cannon
    • 4
  • Marie M. Griffiths
    • 4
  • Ronald L. Wilder
    • 1
  1. 1.Inflammatory Joint Diseases Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, 9000 Rockville Pike, Building 10, Room 9N240, Bethesda, MD 20892, USA
  2. 2.Department of Physiology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799, USA
  3. 3.Division of Autoimmune and Molecular Diseases, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA
  4. 4.Research Service, Veterans Affairs Medical Center and Department of Medicine/Rheumatology, University of Utah, Salt Lake City, UT 84132, USA

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