Mammalian Genome

, Volume 19, Issue 6, pp 420–428

DA rats from two colonies differ genetically and in their arthritis susceptibility



The arthritis-susceptible DA rat is one of the most commonly used rat strains for genetic linkage analysis and is instrumental for the identification of many genetic loci. Even though DA rats were kept as inbred lines at different institutes and suppliers, it became obvious that the various breeding stocks differed genetically. To be able to compare the results from different linkage studies it is very import to verify the genetic background of the substrains used in those studies. We performed a genetic and phenotypic analysis of two DA substrains, DA/ZtmRhd and DA/OlaHsd, and found several genetic differences. One of the allelic differences between the DA/ZtmRhd and the DA/OlaHsd strain was located at rat chromosome 3, a 17-Mb large fragment, including the peak marker of a previously identified quantitative trait locus (QTL) for collagen-induced arthritis, Cia11. In addition, the substrains exhibited a significant difference in the susceptibility to pristane-induced arthritis (PIA) and disease severity of collagen-induced arthritis and PIA. However, by generating and testing a congenic line, we could demonstrate that phenotypic differences were not due to the contaminating fragment on chromosome 3. Nevertheless, we conclude that DA substrains show distinct genetic differences and caution should be taken when comparing arthritis data from different DA substrains.

Supplementary material

335_2008_9125_MOESM1_ESM.xls (71 kb)
(XLS 71 kb)
335_2008_9125_MOESM2_ESM.xls (21 kb)
(XLS 21 kb)


  1. Alamanos Y, Drosos AA (2005) Epidemiology of adult rheumatoid arthritis. Autoimmun Rev 4:130–136PubMedCrossRefGoogle Scholar
  2. Brenner M, Meng HC, Yarlett NC, Joe B, Griffiths MM et al (2005) The non-MHC quantitative trait locus Cia5 contains three major arthritis genes that differentially regulate disease severity, pannus formation, and joint damage in collagen- and pristane-induced arthritis. J Immunol 174:7894–7903PubMedGoogle Scholar
  3. Dieude P, Cornelis F (2005) Genetic basis of rheumatoid arthritis. Joint Bone Spine 72:520–526PubMedCrossRefGoogle Scholar
  4. Dracheva SV, Remmers EF, Gulko PS, Kawahito Y, Longman RE et al (1999) Identification of a new quantitative trait locus on chromosome 7 controlling disease severity of collagen-induced arthritis in rats. Immunogenetics 49:787–791PubMedCrossRefGoogle Scholar
  5. Griffiths MM, Wang J, Joe B, Dracheva S, Kawahito Y et al (2000) Identification of four new quantitative trait loci regulating arthritis severity and one new quantitative trait locus regulating autoantibody production in rats with collagen-induced arthritis. Arthritis Rheum 43:1278–1289PubMedCrossRefGoogle Scholar
  6. Gulko PS, Kawahito Y, Remmers EF, Reese VR, Wang J et al (1998) Identification of a new non-major histocompatibility complex genetic locus on chromosome 2 that controls disease severity in collagen-induced arthritis in rats. Arthritis Rheum 41:2122–2131PubMedCrossRefGoogle Scholar
  7. Hojna S, Kadlecova M, Zicha J, Kunes J (2005) Polymorphism in Nos2 gene is absent in Prague colony of Dahl/Rapp salt-sensitive and salt-resistant rats. Physiol Res 54:201–206PubMedGoogle Scholar
  8. Holm BC, Xu HW, Jacobsson L, Larsson A, Luthman H et al (2001) Rats made congenic for Oia3 on chromosome 10 become susceptible to squalene-induced arthritis. Hum Mol Genet 10:565–572PubMedCrossRefGoogle Scholar
  9. Holmdahl R (1997) Genetic analysis of mouse models for rheumatoid arthritis. In: Textbook of human genome methods. CRC Press, Boca Raton, FLGoogle Scholar
  10. Holmdahl R (2003) Dissection of the genetic complexity of arthritis using animal models. J Autoimmun 21:99–103PubMedCrossRefGoogle Scholar
  11. Holmdahl R, Lorentzen JC, Lu S, Olofsson P, Wester L et al (2001) Arthritis induced in rats with nonimmunogenic adjuvants as models for rheumatoid arthritis. Immunol Rev 184:184–202PubMedCrossRefGoogle Scholar
  12. Joe B (2006) Quest for arthritis-causative genetic factors in the rat. Physiol Genomics 27:1–11PubMedCrossRefGoogle Scholar
  13. Jones RE, Weinberg A, Bourdette D (1994) Evidence for genetic contamination of inbred buffalo rats (RT-1b) obtained from a commercial vendor. J Neuroimmunol 52:215–218PubMedCrossRefGoogle Scholar
  14. Lander ES, Schork NJ (1994) Genetic dissection of complex traits. Science 265:2037–2048PubMedCrossRefGoogle Scholar
  15. Meng HC, Griffiths MM, Remmers EF, Kawahito Y, Li W et al (2004) Identification of two novel female-specific non-major histocompatibility complex loci regulating collagen-induced arthritis severity and chronicity, and evidence of epistasis. Arthritis Rheum 50:2695–2705PubMedCrossRefGoogle Scholar
  16. Miller EJ, Rhodes RK (1982) Preparation and characterization of the different types of collagen. Methods Enzymol 82 Pt A:33–64Google Scholar
  17. Olofsson P, Holmberg J, Pettersson U, Holmdahl R (2003) Identification and isolation of dominant susceptibility loci for pristane-induced arthritis. J Immunol 171:407–416PubMedGoogle Scholar
  18. Olofsson P, Lu S, Holmberg J, Song T, Wernhoff P et al (2003) A comparative genetic analysis between collagen-induced arthritis and pristane-induced arthritis. Arthritis Rheum 48:2332–2342PubMedCrossRefGoogle Scholar
  19. Olofsson P, Johansson A, Wedekind D, Kloting I, Klinga-Levan K et al (2004) Inconsistent susceptibility to autoimmunity in inbred LEW rats is due to genetic crossbreeding involving segregation of the arthritis-regulating gene Ncf1. Genomics 83:765–771PubMedCrossRefGoogle Scholar
  20. Plenge RM, Seielstad M, Padyukov L, Lee AT, Remmers EF et al (2007) TRAF1–C5 as a risk locus for rheumatoid arthritis—a genomewide study. N Engl J Med 357:1199–1209PubMedCrossRefGoogle Scholar
  21. Remmers EF, Longman RE, Du Y, O’Hare A, Cannon GW et al (1996) A genome scan localizes five non-MHC loci controlling collagen-induced arthritis in rats. Nat Genet 14:82–85PubMedCrossRefGoogle Scholar
  22. Saar K, Beck A, Bihoreau MT, Birney E, Brocklebank D et al (2008) SNP and haplotype mapping for genetic analysis in the rat. Nat Genet 40:560–566PubMedCrossRefGoogle Scholar
  23. Smith BD, Martin GR, Miller EJ, Dorfman A, Swarm R (1975) Nature of the collagen synthesized by a transplanted chondrosarcoma. Arch Biochem Biophys 166:181–186PubMedCrossRefGoogle Scholar
  24. The Wellcome Trust Consortium (2007) Genome-wide association study of 14, 000 cases of seven common diseases and 3, 000 shared controls. Nature 447:661–678CrossRefGoogle Scholar
  25. Worthington J (2005) Investigating the genetic basis of susceptibility to rheumatoid arthritis. J Autoimmun 25(suppl):16–20PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Medical Inflammation ResearchBiomedical Center, Lund UniversityLundSweden
  2. 2.Medical Inflammation Research, Department of Medical Biochemistry and BiophysicsKarolinska InstituteStockholmSweden

Personalised recommendations