Animal Models of Sjögren’s Syndrome

  • R. W. Hoffman
  • S. E. Walker


Sjögren’s syndrome was first recognized by Henrich Sjögren (1933) as the triad of keratoconjunctivitis sicca, xerostomia and rheumatoid arthritis. Based upon unique clinical, immunologic and genetic features, two distinct forms of Sjögren’s syndrome, primary and secondary, have since been recognized (Bloch et al. 1965; Fox et al. 1984; Moutsopoulos et al. 1980). The primary form is keratoconjunctivitis sicca associated with xerostomia, whereas secondary Sjögren’s syndrome is the triad of keratoconjunctivitis sicca, xerostomia and a connective tissue disease (Fox et al. 1984; Kaplinsky et al. 1980; McAdam et al. 1976; Whaley and Alspaugh 1985). Sjögren’s syndrome is of interest because it is a common autoimmune disease with significant morbidity (Moutsopoulos et al. 1980). Although extensive studies have provided a large body of information concerning autoantibody production, immune complexes, immunoregulation and immunogenetics, the etiology of Sjögren’s syndrome is not known. Appropriate animal models could greatly advance our understanding of the pathogenesis and treatment of this disorder.


Systemic Lupus Erythematosus Salivary Gland Parotid Gland Lacrimal Gland Nictitate Membrane 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Complete Freund’s Adjuvant


New Zealand Black


New Zealand White


  1. Aguirre GD, Rubin LF, Harvey CE (1971) Keratoconjunctivitis sicca in dogs. J Am Vet Med Assoc 158: 1566–1578PubMedGoogle Scholar
  2. Andrews BS, Eisenberg RA, Theofilopoulos AN et al (1978) Spontaneous murine lupus-like syn-dromes. Clinical and immunopathological manifestations in several strains. J Exp Med 148: 1198–1215PubMedCrossRefGoogle Scholar
  3. Bach M-A, Droz D, Noel L-H et al (1980) Effect of long-term treatment with circulating thymic factor on murine lupus. Arthritis Rheum 23: 1351–1358PubMedCrossRefGoogle Scholar
  4. Bang BG, Bang FB (1968) Localized lymphoid tissues and plasma cells in paraocular and paranasal organ systems in chickens. Am J Pathol 53: 735–751PubMedGoogle Scholar
  5. Bellhorn RW (1981) Laboratory animal ophthalmology. In: Gelatt KN (ed) Veterinary ophthalmology. Lea and Febiger, Philadelphia, pp 649–671Google Scholar
  6. Benedict AA, Tam LQ, Chanh TC et al (1980) Inherited 7 S immunoglobulin deficiency in chickens: Late onset dysgammaglobulinemia and evaluation of the lymphocyte proliferative responses and other immunologic functions. Clin Immunol Immunopathol 17: 1–14PubMedCrossRefGoogle Scholar
  7. Ben-Nun A, Cohen IR (1982) Experimental autoimmune encephalomyelitis (EAE) mediated by T cell lines: Process of selection of lines and characterization of the cells. J Immunol 129: 303–308PubMedGoogle Scholar
  8. Beutner EH, Djanian AY, Geckler RC, Witebsky E (1961) Serological studies of rabbit antibodies to rabbit submaxillary glands. Proc Soc Exp Biol Med 107: 486–491Google Scholar
  9. Bielschowsky M, Helyer BJ, Howie JB (1959) Spontaneous haemolytic anaemia in mice of the NZB/BL strain. Proc Univ Otago Med Sch 37: 9–11Google Scholar
  10. Bloch KJ, Buchanan WW, Wohl MJ, Bunim JJ (1965) Sjögren’s syndrome. A clinical, pathological, and serological study of sixty-two cases. Medicine (Baltimore) 44: 187–231PubMedCrossRefGoogle Scholar
  11. Boss JH, Rosenmann E, Sela J (1977) Experimental allergic sialoadenitis X. Chronic destructive parotitis induced in immunized rats by daily intraductal challenges with antigen. J Oral Pathol 6: 96–105PubMedCrossRefGoogle Scholar
  12. Brightman AH (1980) Keratoconjunctivitis sicca. Vet Med Today 176: 710–711Google Scholar
  13. Carlsoo B, Ostberg Y (1978) Ultrastructural observations on the parotitis autoimmunica in the NZB/NZW hybrid mice. Acta Otolaryngol (Stockh) 85: 298–306Google Scholar
  14. Carlsoo B, Ostberg Y (1979) The autoimmune submandibular sialoadenitis of the NZB/NZW hybrid mice. A light and electron microscopical investigation. Arch Otorhinolaryngol 225: 57–65PubMedCrossRefGoogle Scholar
  15. Chan WC (1964) Experimental sialo-adenitis in guinea-pigs. J Path Bact 88: 592–595PubMedCrossRefGoogle Scholar
  16. Dean DH, Hiramoto RN (1984) Experimental auto-allergic sialoadenitis in male rats. J Oral Pathol 13: 63–68PubMedCrossRefGoogle Scholar
  17. Dishon T, Sela J, Ulmansky M et al (1973) Experimental allergic sialoadenitis VI. Prevention by antihistamine and induction by intraductal instillation of preformed immune complexes. Virchows Arch [Pathol Anat] 359: 283–288Google Scholar
  18. East J (1970) Immunopathology and neoplasms in New Zealand Black (NZB) and SJL-J mice. In: Hamburger F (ed) Progress in experimental tumor research Vol 13. S Karger, Basel, pp 84–134Google Scholar
  19. Eisenbrandt DL, Hubbard GB, Schmidt RE (1982) A subclinical epizootic of sialodacryoadenitis in rats. Lab Anim Sci 32: 655–659PubMedGoogle Scholar
  20. Felsenfeld O (1972) Autoimmune diseases. In: T-W-Fiennes RN (ed) Pathology of simian primates, part I: General pathology. Karger, New York, pp 380–398Google Scholar
  21. Fox RI, Carstens SA, Fong Eet al (1982) Use of monoclonal antibodies to analyze peripheral blood and salivary gland lymphocyte subsets in Sjögren’s syndrome. Arthritis Rheum 25: 419–426PubMedCrossRefGoogle Scholar
  22. Fox RI, Howell FV, Bone RC, Michelson P (1984) Primary Sjögren’s syndrome: Clinical and immunopathologic features. Semin Arthritis Rheum 14: 77–105PubMedCrossRefGoogle Scholar
  23. Gelatt KN, Gwin RM (1981) Canine lacrimal and nasolacrimal systems. In: Gelatt KN (ed) Veterinary ophthalmology. Lea and Febiger, Philadelphia, pp 309–329Google Scholar
  24. Gelatt KN, Peiffer RL, Erickson JL, Gum GG (1968) Evaluation of tear formation in the dog, using a modification of the Schirmer tear test. J Am Vet Med Assoc 166: 368–370Google Scholar
  25. Gershwin ME, Erickson K, Montero J et al (1980) The immunopathology of spontaneously acquired dysgammaglobulinemia in chickens. Clin Immunol Immunopathol 17: 15–30PubMedCrossRefGoogle Scholar
  26. Gershwin ME, Montero J, Eklund J et al (1978) Spontaneous autoimmune disease with associated acquired immune deficiency in chickens. In: Rose NR, Bigazzi PE, Warner NL (eds) Genetic control of autoimmune disease. Elsevier, New York, pp 271–284Google Scholar
  27. Gleichmann E, Van Elven EH, Van der Veen JPW (1982) A systemic lupus erythematosus (SLE)-like disease in mice induced by abnormal T-B cell cooperation. Preferential formation of autoantibodies characteristic of SLE. Eur J Immunol 12: 152–159PubMedCrossRefGoogle Scholar
  28. Gratwhol AA, Moutsopoulos HM, Chused TM et al (1977) Sjögren-type syndrome after allogeneic bone-marrow transplantation. Ann Intern Med 87: 703–706PubMedGoogle Scholar
  29. Greenspan JS, Gutman GA, Weissman IL, Talal N (1974) Thymus-antigen-and immunoglobulin-positive lymphocytes in tissue infiltrates of NZB/NZW mice. Clin Immunol Immunopathol 3: 16–31PubMedCrossRefGoogle Scholar
  30. Haferkamp O (1962) Ein tierexperimenteller Beitrag zur Immunopathologie der Speicheldrüsen. Virchow Arch Path Anat 335: 298–322PubMedCrossRefGoogle Scholar
  31. Hahn BH, Shulman LE (1969) Autoantibodies and nephritis in the white strain ( NZW) of New Zealand mice. Arthritis Rheum 12: 355–364PubMedCrossRefGoogle Scholar
  32. Halliwell REW (1978) Autoimmune disease in the dog. Adv Vet Sci Comp Med 22: 221–263PubMedGoogle Scholar
  33. Halliwell REW (1982) Autoimmune diseases in domestic animals. J Am Vet Med Assoc 181: 1088–1096PubMedGoogle Scholar
  34. Hang L, Theofilopoulos AN, Dixon FJ (1982) A spontaneous rheumatoid arthritis-like disease in MRL/1 mice. J Exp Med 155: 1690–1701PubMedCrossRefGoogle Scholar
  35. Hayashi Y, Sato M, Hirokawa K (1985) Induction of experimental allergic sialadenitis in mice. Am J Pathol 118: 476–483PubMedGoogle Scholar
  36. Hoffman RW, Alspaugh MA, Waggie KS et al (1984) Sjögren’s syndrome in MRL/1 and MRL/n mice. Arthritis Rheum 27: 157–165PubMedCrossRefGoogle Scholar
  37. Hoffman RW, Yang HK, Waggie KS et al (1983) Band keratopathy in MRL/1 and MRL/n mice. Arthritis Rheum 26: 645–652PubMedCrossRefGoogle Scholar
  38. Holoshitz J, Naparstek Y, Ben-Nun A, Cohen IR (1983) Lines of T lymphocytes induce or vaccinate against autoimmune arthritis. Science 219: 56–58PubMedCrossRefGoogle Scholar
  39. Howie JB, Helyer BJ (1965) Autoimmune disease in mice. Ann NY Acad Sci 124: 167–177PubMedCrossRefGoogle Scholar
  40. Howie JB, Helyer BJ (1968) The immunology and pathology of NZB mice. In: Dixon FJ, Kunkel HG (eds) Advances in immunology Vol 9. Academic Press, New York, pp 215–266Google Scholar
  41. Huston DP, Steinberg AD (1979) Animal models of human systemic lupus erythematosus. Yale J Biol Med 52: 289–305PubMedGoogle Scholar
  42. Ichikawa Y, Takaya M, Arimori S (1982) Experimental induction of sialadenitis in rats by heterologous anti-salivary gland antibodies. Tokai J Exp Clin Med 7: 53–61PubMedGoogle Scholar
  43. Innes JRM, Stanton MF (1961) Acute disease of the submaxillary and harderian glands (sialo-dac-ryoadenitis) of rats with cytomegaly and no inclusion bodies. Am J Pathol 38: 455–468PubMedGoogle Scholar
  44. Jonas AM, Craft J, Black CL et al (1969) Sialodacryoadenitis in the rat. A light and electron micro-scopic study. Arch Pathol (Chicago) 88: 613–622PubMedGoogle Scholar
  45. Kaplinsky N, Revach M, Katz WA (1980) Eosinophilic fasciitis: report of a case with features of connective tissue disease. J Rheumatol 7: 536–540PubMedGoogle Scholar
  46. Kaswan RL, Martin CL, Chapman WL (1984) Keratoconjunctivitis sicca: Histopathologic study of nictitating membrane and lacrimal glands from 28 dogs. Am J Vet Res 45: 112–118PubMedGoogle Scholar
  47. Kaswan RL, Martin CL, Dawe DL (1983) Rheumatoid factor determination in 50 dogs with kera-toconjunctivitis sicca. J Am Med Vet Assoc 183: 1073–1075Google Scholar
  48. Kaswan RL, Martin CL, Dawe DL (1985) Keratoconjunctivitis sicca: immunological evaluation of 62 canine cases. Am J Vet Res 46: 376–383PubMedGoogle Scholar
  49. Kelley VE, Winkelstein A (1980) Age-and sex-related glomerulonephritis in New Zealand White mice. Clin Immunol Immunopathol 16: 142–150PubMedCrossRefGoogle Scholar
  50. Kessler HS (1968) A laboratory model for Sjögren’s syndrome. Am J Pathol 52: 671–678PubMedGoogle Scholar
  51. Kessler HS, Cubberly M, Manski W (1971) Eye changes in autoimmune NZB and NZB x NZW mice. Arch Ophthal 85: 211–219PubMedCrossRefGoogle Scholar
  52. Keyes GG, Vickers RA, Kersey JH (1977) Immunopathology of Sjögren-like disease in NZB/NZW mice. J Oral Pathol 6: 288–295PubMedCrossRefGoogle Scholar
  53. Kojima A, Fujinama F, Doi K et al (1980) Isolation and properties of sialodacryoadenitis virus of rats. Exp Anim 29: 409–418Google Scholar
  54. Kurata Y, Watanabe Y, Okada S, Fukuyama Y (1969) Immunological studies of insoluble lipoproteins II. On the salivary gland characteristic antigens. Int Arch Allerg 35: 392–401PubMedCrossRefGoogle Scholar
  55. Lai YL, Jacoby RO, Bhatt PN, Jonas AM (1976) Keratoconjunctivitis associated with sialodacryoadenitis in rats. Invest Ophthalmo1 15: 538–541Google Scholar
  56. Lawley TJ, Peck GL, Moutsopoulos HM et al (1977) Scleroderma, Sjögren-like syndrome, and chronic graft-versus-host disease. Ann Intern Med 87: 707–709PubMedGoogle Scholar
  57. Lewis RM (1974) Spontaneous autoimmune diseases of domestic animals. In: Richter GW, Epstein MA (eds) International review of experimental pathology Vo113. Academic Press, New York, pp 55–82Google Scholar
  58. Lewis RM, Hathaway JE (1967) -Canine systemic lupus erythematosus; presenting with symmetrical polyarthritis. J Small Anim Pract 8: 273–284PubMedCrossRefGoogle Scholar
  59. Ludwig H, Schernthaner G, Scherak O, Kolarz G (1977) Antibodies to pancreatic duct cells in Sjögren’s syndrome and rheumatoid arthritis. Gut 18: 311–315PubMedCrossRefGoogle Scholar
  60. Maron R, Zerubavel R, Friedman A, Cohen IR (1983) T lymphocyte line specific for thyroglobulin produces or vaccinates against autoimmune thyroiditis in mice. J Immuno1131: 2316–2322Google Scholar
  61. McAdam LP, O’Hanlan MA, Bluestone R, Pearson CM (1976) Relapsing polychondritis: pro-spective study of 23 patients and a review of the literature. Medicine (Baltimore) 55: 193–215CrossRefGoogle Scholar
  62. McCabe BF (1961) The evidence for an auto-immune mechanism in Mikulicz’s disease. Laryngo-scope 71: 396–403CrossRefGoogle Scholar
  63. Montero J, Gershwin ME, Eklund J et al (1979) Autoimmune manifestations of selective 7S immunoglobulin deficiency of chickens. Clin Immunol Immunopathol 14: 334–347PubMedCrossRefGoogle Scholar
  64. Moutsopoulos HM, Chused TM, Mann DL et al (1980) Sjögren’s syndrome (sicca syndrome): current issues. Ann Intern Med 92: 212–226PubMedGoogle Scholar
  65. Moutsopoulos HM, Klippel JH, Pavlidis N et al (1980) Correlative histologic and serologic findings of sicca syndrome in patients with systemic lupus erythematosus. Arthritis Rheum 23: 36–40PubMedCrossRefGoogle Scholar
  66. Murphy ED (1981) Lymphoproliferation (lpr) and other single-locus models for murine lupus. In: Gershwin ME, Merchant B (eds) Immunological defects in laboratory animals Vol 2. Plenum, New York, pp 143–173CrossRefGoogle Scholar
  67. Naparstek Y, Ben-Nun A, Holoshitz J et al (1983) T lymphocyte lines producing or vaccinating against autoimmune encephalomyelitis (EAE). Functional activation induces peanut agglutinin receptors and accumulation in the brain and thymus of line cells. Eur J Immunol 13: 418–423PubMedCrossRefGoogle Scholar
  68. Newton CD, Lipowtiz M, Halliwell RE et al (1976) Rheumatoid arthritis in dogs. J Am Vet Med Assoc 168: 113–121PubMedGoogle Scholar
  69. O’Sullivan FX, Fassbender H-G, Gay S, Koopman WJ (1985) Etiopathogenesis of the rheumatoid arthritis-like disease in MRL/1 mice. I. The histomorphologic basis of joint destruction. Arthritis Rheum 28: 529–536PubMedCrossRefGoogle Scholar
  70. Pals ST, Radaszkiewicz T, Gleichmann E (1984) Allosuppressor-and allohelper-T cells in acute and chronic graft-versus-host disease. J Immunol 132: 1669–1678PubMedGoogle Scholar
  71. Pedersen NC, Pool RC, Castles JJ, Weisner K (1976) Noninfectious canine arthritis: rheumatoid arthritis. J Am Vet Med Assoc 169: 295–303PubMedGoogle Scholar
  72. Quimby FW, Schwartz RS, Poskitt T, Lewis RM (1979) A disorder of dogs resembling Sjögren’s syndrome. Clin Immunol Immunopathol 12: 471–476PubMedCrossRefGoogle Scholar
  73. Ramos-Niembro F, Alarcon-Segovia D (1979) Development of sicca symptoms in systemic lupus erythematosus patients with existing subclinical abnormalities of lacrimal and/or salivary glands. Arthritis Rheum 22: 935–936PubMedCrossRefGoogle Scholar
  74. Rosenmann E, Sela J, Ulmansky M et al (1974) Experimental allergic sialoadenitis II. Induction of acute sialoadenitis in rats by locally administered basement membrane antibodies. Oral Surg 37: 566–575PubMedCrossRefGoogle Scholar
  75. Ruskell GL (1969) Changes in nerve terminals and acini of the lacrimal gland and changes in secretion induced by autonomic denervation. Z Zellforsch 94: 261–281PubMedCrossRefGoogle Scholar
  76. Schot LPC, Verheul HAM, Schuurs AHWM (1984) Effect of nandrolone decanoate on Sjögren’s syndrome like disorders in NZB/NZW mice. Clin Exp Immunol 57: 571–574PubMedGoogle Scholar
  77. Schumacher HR, Newton C, Halliwell REW (1980) Synovial pathologic changes in spontaneous canine rheumatoid-like arthritis. Arthritis Rheum 23: 412–423PubMedCrossRefGoogle Scholar
  78. Sela J, Bab JA, Dishon T et al (1975) Experimental allergic sialoadenitis. VII. Reactivity of the parotid gland to antigenic challenge in passively immunized rats. J Oral Pathol 4: 11–18PubMedCrossRefGoogle Scholar
  79. Sela J, Dishon T, Rosenmann E et al (1973) Experimental allergic sialoadenitis V. Comparison of the response of the parotid gland and synovial membrane to multiple antigenic challenges. J Oral Pathol 2: 7–15PubMedCrossRefGoogle Scholar
  80. Sela J, Ulmansky M, Dishon T et al (1972) Experimental allergic sialoadenitis I. Acute sialoadenitis induced by a local immune reaction. Virchows Arch [Pathol Anat] 335: 213–219Google Scholar
  81. Sharawy M, White SC (1978) Morphometric and fine structural study of experimental autoallergic sialadenitis of rat submandibular glands. Virchows Arch [Cell Pathol] 28: 255–273Google Scholar
  82. Shulman HM, Sale GE, Lerner KG et al (1978) Chronic cutaneous graft-versus-host disease in man. Am J Pathol 91: 545–564PubMedGoogle Scholar
  83. Sjögren H (1933) Zur Kenntnis der keratoconjunctivitis sicca. Acta Ophthalmol [Suppl] (Copenh) 11: 48–97Google Scholar
  84. Slatter DH, Blogg JR (1978) Keratoconjunctivitis sicca in dogs associated with sulphonamide administration. Aust Vet J 54: 444–446PubMedCrossRefGoogle Scholar
  85. Takeda Y, Ishikawa G (1983) Experimental autoallergic sialadenitis in mice: Histopathological and ultrastructural studies. Virchows Arch [Pathol Anat] 400: 143–154CrossRefGoogle Scholar
  86. Takeda Y, Komori A, Ishikawa G (1981) Histopathological study of the salivary glands in SL/Ni mice. Jpn J Oral Biol 23: 427–438CrossRefGoogle Scholar
  87. Teichert VG (1966) Plasmazellulare Infiltration des dritten Augenlides beim Hund. Berl München Tieraerzl Wschr 79: 449–451Google Scholar
  88. Theofilopoulos AN, Dixon FJ (1985) Murine models of systemic lupus erythematosus. In: Dixon FJ (ed) Advances in immunology Vol 37. Academic Press, New York, pp 269–390Google Scholar
  89. Theofilopoulos AN, McConahey PJ, Izui S et al (1980) A comparative immunologic analysis of several murine strains with autoimmune manifestations. Clin Immunol Immunopathol 15: 258–278PubMedCrossRefGoogle Scholar
  90. Ulmansky M, Dishon T, Rosenmann E et al (1972) Experimental allergic sialoadenitis IV. Studies on the etiopathogenetic mechanisms of the acute and chronic inflammatory process. Isr J Med Sci 8: 1791–1797PubMedGoogle Scholar
  91. Van Rappard-Van der Veen FM, Kiesel U, Poels L et al (1984) Further evidence against random polyclonal antibody formation in mice with lupus-like graft-vs-host disease. J Immuno11 32: 1814–1820Google Scholar
  92. Weill JC, Goldberg M (1976) Intracellular modifications induced in mouse submaxillary glands by antibodies directed against saliva. Immunology 31: 397–405PubMedGoogle Scholar
  93. Whaley K, Alspaugh MA (1985) Sjögren’s syndrome. In: Kelley WN, Harris ED, Ruddy S, Sledge CB (eds) Textbook of rheumatology, 2nd ed. Saunders, Philadelphia, pp 956–978Google Scholar
  94. Whaley K, MacSween RNM (1974) Experimental induction of immune sialadenitis in guinea-pigs using different adjuvants. Clin Exp Immuno117: 681–684Google Scholar
  95. White SC, Casarett GW (1974) Induction of experimental autoallergic sialadenitis. J Immuno1112: 178–185Google Scholar
  96. White SC (1976) T-cell dependence of experimental autoallergic lesions of rat submandibular glands. J Dent Res 55: B 299 (abstract)Google Scholar

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© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • R. W. Hoffman
  • S. E. Walker

There are no affiliations available

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