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Rheumatoid arthritis: identifying and characterising polymorphisms using rat models.

Anthony C Y Yau1, Rikard Holmdahl2

  • 1Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.

Disease Models & Mechanisms
|October 14, 2016
PubMed
Summary

Rat models are crucial for understanding rheumatoid arthritis (RA) genetics. Congenic strains help identify genes contributing to RA, offering new insights into human disease mechanisms.

Keywords:
Chronic inflammationCongenic mappingGeneticsRat modelsRheumatoid arthritisSusceptibility genes

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Area of Science:

  • Genetics
  • Immunology
  • Rheumatology

Background:

  • Rheumatoid arthritis (RA) is a chronic inflammatory joint disease with genetic and environmental influences.
  • Current treatments lack preventative capabilities, and cures are unavailable.
  • Genome-wide association studies (GWAS) identified RA risk loci, but their pathogenic roles remain largely unknown.

Purpose of the Study:

  • To discuss the utility of rat models in identifying quantitative trait loci (QTLs) for rheumatoid arthritis.
  • To highlight the role of congenic strains in positional cloning of causative genes.
  • To explore how these models provide biological insights into human RA.

Main Methods:

  • Genetic linkage analysis in rat models to detect QTLs.
  • Use of congenic strains to isolate specific genetic loci on a fixed background.
  • Positional cloning to identify causative genes within QTLs.

Main Results:

  • Congenic strains overcome genetic heterogeneity and environmental interactions present in human studies.
  • Functional studies in congenic strains enabled the discovery of major genes contributing to rat arthritis.
  • These findings offer valuable biological insights applicable to human rheumatoid arthritis.

Conclusions:

  • Rat models, particularly congenic strains, are powerful tools for dissecting the genetic architecture of rheumatoid arthritis.
  • This approach facilitates the identification and functional characterization of RA-associated genes.
  • Advances in rat models contribute significantly to understanding the pathogenesis of human rheumatoid arthritis.