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Animal Models of Spondyloarthritis

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Molecular Mechanisms of Spondyloarthropathies

Part of the book series: Advances in Experimental Medicine and Biology ((volume 649))

Abstract

Animal models are available for the study of several different aspects of spondyloarthritis. The models include naturally occurring spontaneous disorders in primates and rodents, spontaneous disorders in transgenic or gene-deleted rodents and induced disorders in rodents. Areas of investigation to which these models contribute include the role HLA-B27, processes of spinal and peripheral joint inflammation and calcification, immune responses to candidate antigens and the role of TNF.

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References

  1. Urvater JA, McAdam SN, Loehrke JH et al. A high incidence of Shigella-induced arthritis in a primate species: major histocompatibility complex class I molecules associated with resistance and susceptibility and their relationship to HLA-B27. Immunogenetics 2000; 51:314–325.

    Article  PubMed  CAS  Google Scholar 

  2. Urvater JA, Hickman H, Dzuris JL et al. Gorillas with spondyloarthropathies express an MHC class I molecule with only limited sequence similarity to HLA-B27 that binds peptides with arginine at P2. J Immunol 2001; 166:3334–3344.

    PubMed  CAS  Google Scholar 

  3. Sokoloff L, Snell KC, Stewart HL. Spinal ankylosis in old Rhesus monkeys. Clin Orthop Relat Res 1968; 61:285–293.

    Article  PubMed  CAS  Google Scholar 

  4. Adams RF, Flinn GS, Jr, Douglas M. Ankylosing spondylitis in a nonhuman primate: a monkey tale. Arthritis Rheum 1987; 30:956–957.

    Article  PubMed  CAS  Google Scholar 

  5. Swezey RL, Cox C, Gonzales B. Ankylosing spondylitis in nonhuman primates: the drill and the siamang. Semin Arthritis Rheum 1991; 21:170–174.

    Article  PubMed  CAS  Google Scholar 

  6. Rothschild BM, Woods RJ. Spondyloarthropathy as an Old World phenomenon. Semin Arthritis Rheum 1992; 21:306–316.

    Article  PubMed  CAS  Google Scholar 

  7. Rothschild BM, Ruhli FJ. Comparison of arthritis characteristics in lowland Gorilla gorilla and mountain Gorilla beringei. Am J Primatol 2005; 66:205–218.

    Article  PubMed  Google Scholar 

  8. Sobao Y, Tsuchiya N, Takiguchi M et al. Overlapping peptide-binding specificities of HLA-B27 and B39: evidence for a role of peptide supermotif in the pathogenesis of spondylarthropathies. Arthritis Rheum 1999; 42:175–181.

    Article  PubMed  CAS  Google Scholar 

  9. Lawlor DA, Warren E, Taylor P et al. Gorilla class I major histocompatibility complex alleles: comparison to human and chimpanzee class I. J Exp Med 1991; 174:1491–1509.

    Article  PubMed  CAS  Google Scholar 

  10. Balla Jhagjhoorsingh SS, Koopman G, Mooij P et al. Conserved CTL epitopes shared between HIV-infected human long-term survivors and chimpanzees. J Immunol 1999; 162:2308–2314.

    PubMed  CAS  Google Scholar 

  11. Glant TT, Mikecz K, Arzoumanian A et al. Proteoglycan-induced arthritis in BALB/c mice. Clinical features and histopathology. Arthritis Rheum 1987; 30:201–212.

    Article  PubMed  CAS  Google Scholar 

  12. Leroux JY, Guerasimov A, Cartman A et al. Immunity to the G1 globular domain of the cartilage proteoglycan aggrecan can induce inflammatory erosive polyarthritis and spondylitis in BALB/c mice but immunity to G1 is inhibited by covalently bound keratan sulfate in vitro an vi vivo. J Clin Invest 1996; 97:621–632.

    Article  PubMed  CAS  Google Scholar 

  13. Shi S, Ciurli C, Cartman A et al. Experimental immunity to the G1 domain of the proteoglycan versican induces spondylitis and sacroiliitis, of a kind seen in human spondylarthropathies. Arthritis Rheum 2003; 48:2903–2915.

    Article  PubMed  CAS  Google Scholar 

  14. Szabo Z, Szanto S, Vegvari A et al. Genetic control of experimental spondylarthropathy. Arthritis Rheum 2005; 53:2452–2460.

    Article  Google Scholar 

  15. Zhang Y, Guerassimov A, Leroux JY et al. Induction of arthritis in BALB/c mice by cartilage link protein: involvement of distinct regions recognized by T and B-lymphocytes. Am J Pathol 1998; 153:1283–1291.

    Article  PubMed  CAS  Google Scholar 

  16. Zou J, Appel H, Rudwaleit M et al. Analysis of the CD8+ T-cell response to the G1 domain of aggrecan in ankylosing spondylitis. Ann Rheum Dis 2005; 64:722–729.

    Article  PubMed  CAS  Google Scholar 

  17. Kuon W, Kuhne M, Busch DH et al. Identification of novel human aggrecan T-cell epitopes in HLA-B27 transgenic mice associated with spondyloarthropathy. J Immunol 2004; 173:4859–4866.

    PubMed  CAS  Google Scholar 

  18. Vegvari A, Szabo Z, Szanto S et al. Two major interacting chromosome loci control diseae susceptibility in murine model of spondyloarthropathy. J Immunol 2005; 175:2475–2483.

    PubMed  CAS  Google Scholar 

  19. Bardos T, Szabo Z, Czipri M et al. A longitudinal study on an autoimmune murine model of ankylosing spondylitis. Ann Rheum Dis 2005; 64:981–987.

    Article  PubMed  CAS  Google Scholar 

  20. Zhang Y. Animal models of inflammatory spinal and sacroiliac joint diseases. Rheum Dis Clin North Am 2003; 29:631–645.

    Article  PubMed  Google Scholar 

  21. Adraichev VA, Glant TT. Experimental spondyloarthropathies: animal models of ankylosing spondylitis. Curr Rheumatol Rep 2006; 8:267–274.

    Article  Google Scholar 

  22. Mahowald ML, Krug H, Taurog J. Progressive ankylosis in mice. An animal model of spondylarthropathy I. Clinical and radiographic findings. Arthritis Rheum 1988; 31:1390–1399.

    Article  PubMed  CAS  Google Scholar 

  23. Ho AM, Johnson MD, Kingsley DM, Role of the mouse ank gene in control of tissue calcification and arthritis. Science 2000; 289:265–270.

    Article  PubMed  CAS  Google Scholar 

  24. Gurley KA, Reimer RJ, Kingsley DM. Biochemical and genetic analysis of ANK in arthritis and bone disease. Am J Hum Genet 2006; 79:1017–1029.

    Article  PubMed  CAS  Google Scholar 

  25. Harmey D, Hessle L, Narisawa S et al. Concerted regulation of inorganic pyrophosphate and osteopontin by akp2, enpp1 and ank: an integrated model of the pathogensis of mineralization disorders. Am J Pathol 2004; 164:1199–1209.

    Article  PubMed  CAS  Google Scholar 

  26. Gurley KA, Chen H, Guenther C et al. Mineral formation in joints caused by complete or joint-specific loss of ANK function. J Bone Miner Res 2006; 21:1238–1247.

    Article  PubMed  CAS  Google Scholar 

  27. Williams CJ, Pendleton A, Bonavita G et al. Mutations in the amino terminus and ANKH in two US families with calcium pyrophosphate dihydrate crystal deposition disease. Arthritis Rheum 2003; 48:2627–2631.

    Article  PubMed  CAS  Google Scholar 

  28. Reichenberger E, Tiziani V, Watanabe S et al. Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the transmembrane protein ANK. Am J Hum Genet 2001; 68:1321–1326.

    Article  PubMed  CAS  Google Scholar 

  29. Malkin I, Dahm S, Suk A et al. Association of ANKH gene polymorphisms with radiographic hand bone size and geometry in a Chuvasha population. Bone 2005; 36:365–373.

    Article  PubMed  CAS  Google Scholar 

  30. Timms AE, Zhang Y, Bradbury L et al. Investigation of the role of ANKH in ankylosing spondylitis. Arthritis Rheum 2003; 48:2898–2902.

    Article  PubMed  CAS  Google Scholar 

  31. Tsui FW, Tsui HW, Cheng EY et al. Novel genetic markers in the 5′-flanking region of ANKH are associated with ankylosing spondylitis. Arthritis Rheum 2003; 48:791–797.

    Article  PubMed  CAS  Google Scholar 

  32. Tsui HW, Inman RD, Paterson AD et al. ANKH variants associated with ankylosing spondylitis: gender differences. Arthritis Res Ther 2005; 7:R513–525.

    Article  PubMed  CAS  Google Scholar 

  33. Ivanyi P, Eulderink F, van Alphen L et al. Joint disease in HLA-B27 transgenic mice. In: Lipsky P, Taurog JD, eds. HLA-B27 + Spondyloarthropathies. New York: Elsevier, 1991: 71–78.

    Google Scholar 

  34. Weinreich S, Eulderink F, Capkova J et al. HLA-B27 as a relative risk factor in ankylosing enthesopathy in transgenic mice. Hum Immunol 1995; 42:103–115.

    Article  PubMed  CAS  Google Scholar 

  35. Eulderink F, Ivanyi P, Weinreich S. Histopathology of murine ankylosing enthesopathy. Pathol Res Pract 1998; 194:797–803.

    Article  PubMed  CAS  Google Scholar 

  36. Rehakova Z, Capkova J, Stepankova R et al. Germ-free mice do not develop ankylosing enthesopathy, a spontaneous joint disease. Hum Immunol 2000; 61:555–558.

    Article  PubMed  CAS  Google Scholar 

  37. Nordling C, Karlsson-Parra A, Jansson L et al. Characterization of a spontaneously occurring arthritis in male DBA/1 mice. Arthritis Rheum 1992; 35:717–722.

    Article  PubMed  CAS  Google Scholar 

  38. Corthay A, Hansson AS, Holmdahl R. T-lymphocytes are not required for the spontaneous development of entheseal ossification leading to marginal ankylosis in the DBA/1 mouse. Arthritis Rheum 2000; 43:844–851.

    Article  PubMed  CAS  Google Scholar 

  39. Lories RJ, Matthys P, de Vlam K et al. Ankylosing enthesitis, dactylitis and onychoperiostitis in male DBA/1 mice: a model of psoriatic arthritis. Ann Rheum Dis 2004; 63:595–598.

    Article  PubMed  CAS  Google Scholar 

  40. Lories RJ, Derese I, de Bari C et al. Evidence for uncoupling of inflammation and joint remodeling in a mouse model of spondylarthritis. Arthritis Rheum 2007; 56:489–497.

    Article  PubMed  Google Scholar 

  41. Schett G, Landewe R, van der Heijde D. Tumour necrosis factor blockers and structural remodelling in ankylosing spondylitis: what is reality and what is fiction? Ann Rheum Dis 2007; 66:709–711.

    Article  PubMed  CAS  Google Scholar 

  42. Lories RJ, Derese I, Luyten FP. Modulation of bone morphogenetic protein signaling inhibits the onset and progression of ankylosing enthesitis. J Clin Invest 2005; 115:1571–1579.

    Article  PubMed  CAS  Google Scholar 

  43. Capkova J, Ivanyi P, Rehakova Z. Sexual dimorphism, but not testosterone itself, is responsible for ankylosing enthesitis of the ankle in B10.BR (H-2k) male mice. Ann Rheum Dis 2006; 65:130–132.

    Article  PubMed  CAS  Google Scholar 

  44. Khare SD, Luthra HS, David CS. Spontaneous inflammatory arthritis in HLA-B27 transgenic mice lacking beta 2-microglobulin: a model of human spondyloarthropathies. J Exp Med 1995; 182:1153–1158.

    Article  PubMed  CAS  Google Scholar 

  45. Khare SD, Lee S, Bull MJ et al. Spontaneous inflammatory disease in HLA-B27 transgenic mice does not require transporter of antigenic peptides. Clin Immunol 2001; 98:364–369.

    Article  PubMed  CAS  Google Scholar 

  46. Kingsbury DJ, Mear JP, Witte DP et al. Development of spontaneous arthritis in beta2-microglobulin-deficient mice without expression of HLA-B27: association with deficiency of endogenous major histocompatibility complex class I expression. Arthritis Rheum 2000; 43:2290–2296.

    Article  PubMed  CAS  Google Scholar 

  47. Keffer J, Probert L, Cazlaris H et al. Transgenic mice expressing human tumor necrosis factor: a predictive genetic model of arthritis. Embo J 1991; 10:4025–4031.

    PubMed  CAS  Google Scholar 

  48. Redlich K, Gortz B, Hayer S et al. Overexpression of tumor necrosis factor causes bilateral sacroiliitis. Arthritis Rheum 2004; 50:1001–1005.

    Article  PubMed  CAS  Google Scholar 

  49. Diarra D, Stolina M, Polzer K et al. Dicklopf-1 is a master regulator of joint remodeling. Nat Med 2007; 13:156–163.

    Article  PubMed  CAS  Google Scholar 

  50. Krimpenfort P, Rudenko G, Hochstenbach F et al. Crosses of two independenently derived transgenic mice demonstrate functional complementation of the genes encoding heavy (HLA-B27) and light (beta 2-microglobulin) chains of HLA class I antigens. Embo J 1987; 6:1673–1676.

    PubMed  CAS  Google Scholar 

  51. Hammer RE, Maika SD, Richardson JA et al. Spontaneous inflammatory disese in transgenic rats expressing HLA-B27 and human beta 2m: an animal model of HLA-B27-associated human disorders. Cell 1990; 63:1099–1112.

    Article  PubMed  CAS  Google Scholar 

  52. Taurog JD, Maika SD, Simmons WA et al. Susceptibility to inflammatory disease in HLA-B27 transgenic rat lines correlates with the level of B27 expression. J Immunol 1993; 150:4168–4178.

    PubMed  CAS  Google Scholar 

  53. Taurog JD, Maika SD, Satumtira N et al. Inflammatory disease in HLA-B27 transgenic rats. Immunol Rev 1999; 169:209–223.

    Article  PubMed  CAS  Google Scholar 

  54. Taurog JD, Richardson JA, Croft JT et al. The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J Exp Med 1994; 180:2359–2364.

    Article  PubMed  CAS  Google Scholar 

  55. Breban M, Hammer RE, Richardson JA et al. Transfer of the inflammtory disease of HLA-B27 transgenic rats by bone marrow engraftment. J Exp Med 1993; 178:1607–1616.

    Article  PubMed  CAS  Google Scholar 

  56. Breban M, Fernandez-Sueiro JL, Richardson JA et al. T-cells, but not thymic exposure to HLA-B27, are required for the inflammatory disease of HLA-B27 transgenic rats. J Immunol 1996; 156:794–803.

    PubMed  CAS  Google Scholar 

  57. Qian BF, Tonkonogy SL, Hoentjen F et al. Dysregulated luminal bacterial antigen-specific T-cell responses and antigen-presenting cell function in HLA-B27 transgenic rats with chronic colitis. Immunology 2005; 116:112–121.

    Article  PubMed  CAS  Google Scholar 

  58. Dangoria NS, DeLay ML, Kingsbury DJ et al. HLA-B27 misfolding is associated with aberrant intermolecular disulfide bond formation (dimerization) in the endoplasmic reticulum. J Biol Chem 2002; 277:23459–23468.

    Article  PubMed  CAS  Google Scholar 

  59. Tran TM, Satumtira N, Dorris ML et al. HLA-B27 in transgenic rats forms disulfide-linked heavy chain oligomers and multimers that bind to the chaperone BiP. J Immunol 2004; 172:5110–5119.

    PubMed  CAS  Google Scholar 

  60. Kollnberger S, Bird LA, Roddis M et al. HLA-B27 heavy chain homodimers are expressed in HLA-B27 transgenic rodent models of spondyloarthritis and are ligands for paired Ig-like receptors. J Immunol 2004; 173:1699–1710.

    PubMed  CAS  Google Scholar 

  61. Kollnberger S, Chan A, Sun MY et al. Interaction of HLA-B27 homodimers with KIR3DL1 and KIR3DL2, unlike HLA-B27 heterotrimers, is independent of the sequence of bound peptide. Eur J Immunol 2007; 37:1313–1322.

    Article  PubMed  CAS  Google Scholar 

  62. Turner MJ, Delay ML, Bai S et al. HLA-B27 up-regulation causes accumulation of misfolded heavy chains and correlates with the magnitude of the unfolded protein response in transgenic rats: Implications for the pathogenesis of spondylarthritis-like disease. Arthritis Rheum 2007; 56:215–223.

    Article  PubMed  Google Scholar 

  63. Tran TM, Dorris ML, Satumtira N et al. Additional human beta2-microglobulin curbs HLA-B27 misfolding and promotes arthritis and spondylitis without colitis in male HLA-B27-transgenic rats. Arthritis Rheum 2006; 54:1317–1327.

    Article  PubMed  CAS  Google Scholar 

  64. Taurog JD. Ankylosing spondylitis: new improved treatment, new improved models. Drug Discovery Today 2006; 3:27–31.

    Article  Google Scholar 

  65. Stagg AJ, Breban M, Hammer RE et al. Defective dendritic cell (DC) function in a HLA-B27 transgenic rat model of spondyloarthropathy (SpA). Adv Exp Med Biol 1995; 378:557–559.

    Article  PubMed  CAS  Google Scholar 

  66. Hacquard Bouder C, Falgarone G, Bosquet A et al. Defective costimulatory function is a striking feature of antigen-presenting cells in an HLA-B27-transgenic rat model of spondylarthropathy. Arthritis Rheum 2004; 50:1624–1635.

    Article  PubMed  CAS  Google Scholar 

  67. Hacquard Bouder C, Chimenti MS, Giquel B et al. Alteration of antigen-independent immunologic synapse formation between dendritic cells from HLA-B27-transgenic rats and CD4+ T-cells: selective impairment of costimulatory molecule engagement by mature HLA-B27. Arthritis Rheum 2007; 56:1478–1489.

    Article  PubMed  Google Scholar 

  68. Fert I, Glatigny S, Poulain C et al. Dendritic cells (DCs) functional defect correlates with spondyloarthritis (SpA) phenotype in HLA-B27/human β2-microglobulin (hβ2m) transgenic rat lines. Arthritis Rheum 2007; 56:S247 (abstract).

    Google Scholar 

  69. Lories RJ. Animal models of spondyloarthritis. Curr Opin Rheumatol 2006; 18:342–346.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Rheumatic Diseases Division, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390-8884, USA

    Joel D. Taurog

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  1. Joel D. Taurog
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  1. Hospital Universitario Central de Asturias, Oviedo, Spain

    Carlos López-Larrea PhD  & Roberto Díaz-Peña BSc  & 

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Taurog, J.D. (2009). Animal Models of Spondyloarthritis. In: López-Larrea, C., Díaz-Peña, R. (eds) Molecular Mechanisms of Spondyloarthropathies. Advances in Experimental Medicine and Biology, vol 649. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0298-6_18

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