Genetic heterogeneity in rheumatoid arthritis mouse models induced by extrinsic and intrinsic factors

Shinichi Mizuki, Hisashi Oishi, Ming Cai Zhang, Junji Kamogawa, Tatsuhiko Miyazaki, Masao Ono, Satoru Takahashi, Haruyasu Yamamoto, Masato Nose

Research output: Contribution to journalArticlepeer-review

Abstract

A cumulative effect of the susceptibility genes with polymorphic alleles may be responsible for rheumatoid arthritis (RA). The objective of this study was to clarify whether susceptibility to RA is under the control of common allelic loci between two different RA models induced by extrinsic and intrinsic factors, collagen-induced arthritis (CIA) in DBA/1 mice and arthritis in MRL/Mp (MRL) mice associated with the Fas deficient mutant gene, Faslpr, respectively. CIA was examined in mice of parental DBA/1 and MRL, (MRL × DBA/1) F1 and (MRL × DBA/1) F2 progenies. In genome-wide screening of the severity in the F2 using microsatellite markers, significant linkage was observed on chromosomes 5 and 17 at map position of D5Mit259 and H-2, respectively, associated with DBA/1 alleles, while there was no loci associated with arthritis of MRL-Faslpr mice previously identified. In a quantitative trait locus (QTL) analysis, the locus on chromosome 5 showed the highest peak at map position 35 cM (LOD score 6.0). This study may indicate that the arthritis induced by extrinsic and intrinsic factors is under the control of a different combination of susceptibility genes with common and different alleles, possibly simulating the genetic heterogeneity of RA.

Original languageEnglish
Pages (from-to)430-437
Number of pages8
JournalPathology international
Volume60
Issue number6
DOIs
Publication statusPublished - 2010 Jun

Keywords

  • CIA
  • DBA/1
  • MHC
  • MRL
  • Quantitative trait locus (QTL)
  • Susceptibility locus

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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