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Identification of new loci controlling collagen-induced arthritis in mouse using a partial advanced intercross and congenic strains

Författare

  • M. Popovic
  • Emma Ahlqvist
  • Eszter Rockenbauer
  • Robert Bockermann
  • R. Holmdahl

Summary, in English

Collagen-induced arthritis (CIA) is a well studied mouse model of the human disease rheumatoid arthritis (RA). Both CIA and RA are complex diseases affected by multiple genes as well as environmental factors. Identifying the genes that determine susceptibility to arthritis would give invaluable clues to the largely unknown aetiology of RA. In this study, we dissected a known locus, Cia6, as well as a genomic region on chromosome 14 with no previously known arthritis loci, using a partial advanced intercross and a collection of congenic strains. The chromosome 14 congenic fragment, containing the T-cell receptor alpha (Tcra) locus, was included based on the hypothesis that the Cia6 locus is caused by a polymorphism in the Tcr beta (Tcrb) locus and that the two loci interact. Splitting up the congenic fragments revealed multiple loci affecting arthritis traits as well as production of collagen-specific autoantibodies. In total seven new loci were identified of which four were in the previously unlinked chromosome 14 region. Both Tcr loci were within CIA loci making them candidate susceptibility genes. The results demonstrate the importance of breaking up genetic regions in smaller fragments to identify the underlying complex set of loci.

Avdelning/ar

  • Immunology

Publiceringsår

2008

Språk

Engelska

Sidor

405-413

Publikation/Tidskrift/Serie

Scandinavian Journal of Immunology

Volym

68

Issue

4

Dokumenttyp

Artikel i tidskrift

Förlag

Wiley-Blackwell

Ämne

  • Immunology in the medical area

Status

Published

Forskningsgrupp

  • Immunology

ISBN/ISSN/Övrigt

  • ISSN: 1365-3083