Numerous models of exocrine tissue pathology related to autoimmune initiation of disease have been described, primarily by either immunohistology or histopathology. These model systems include inbred mouse strains that develop systemic lupus erythematosus, rheumatoid arthritis, graft vs. host disease, and diabetes. Commonly observed features of these mice include organized lymphocytic foci, composed of CD4+ and CD8+ T-cells, in both the salivary and the lacrimal glands. However, only the diabetic mouse model (NOD) undergoes a corresponding loss in exocrine gland function related to the presence of lymphocytic infiltrates. As we define the underlying pathophysiology of Sjögren's syndrome, the future of animal models for this disease will involve genetic exploration of candidate genes for development of autoimmune exocrinopathy.
Carlsten H., Nilsson N., Jonsson R., Bäckman K., Holmdahl R., Tarkowski A. (1992). Estrogen accelerates immune complex glomerulonephritis but ameliorates T-cell mediated vasculitis and sialoadenitis in autoimmune MRL lpr/lpr mice. Cell Immunol144:190-202.
2.
Cutler LS, Rozenski D., Coolens J., Rozing J., Angelillo M., Wayne AL, et al. (1991). Experimental autoallergic sialoadenitis in the LEW rat 1. Parameters of disease induction. Cell Immunol135:335-345.
3.
Fox RI, Kang H.-I (1992). Pathogenesis of Sjögren's syndrome. Rheum Dis Clin North Am18:517-538.
4.
Garchon H-J., Luan J.-J, Eloy L., Bédossa P., Bach JF ( 1994). Genetic analysis of immune dysfunction in non-obese diabetic (NOD) mice: mapping of a susceptibility locus close to the bcl-2 gene correlates with increased resistance of NOD T cells to apoptosis induction. Eur J Immunol24:380-384.
5.
Goillot E., Mutin M., TouraineJ-L (1991). Sialoadenitis in nonobese diabetic mice: transfer into syngeneic healthy neonates by splenic T lymphocytes. Clin Immunol Immunopathol59:462-473.
6.
Gottlieb PA, Rossini AA, Mordes JP (1988). Approaches to prevention and treatment of IDDM in animal models. Diabetes Care11(Suppl 1):29-36.
7.
Greiner DL, Angelillo M., Wayne AL, Fitzgerald KM, Rozenski D., Cutler LS (1991). Experimental autoallergic sialoadenitis in the LEW rat III. Role of CD4+ T cells in EAS induction. Cell Immunol135:354-359.
8.
Hashim GA, Day ED (1988). Role of antibodies in T cell-mediated experimental allergic encephalomyelitis. J Neurosci Rev21:1-5.
9.
Hayashi Y., Haneji N., Hanamo H., Yanagi K. (1994). Transfer of Sjogren's syndrome-like autoimmune lesions into SCID mice and prevention of lesions by anti-CD4 and anti-T cell receptor antibody. Eur J Immunol24:2826-2831.
10.
Hu Y., Nakagawa Y., Purushotham KR, Humphreys-Beher MG (1992). Functional changes in salivary glands of autoimmune disease-prone NOD mice. Am J Physiol263:E607-E614.
11.
Hu Y., Purushotham KR, Wang P., Dawson R. Jr, Humphreys-Beher MG (1994). Down-regulation of β-adrenergic receptors and signal transduction response in salivary glands of NOD mice. Am J Physiol266:G433-G443.
12.
Humphreys-Beher MG, Brinkley L., Purushotham KR, Wang P.-L, Nakagawa Y., Dusek D., et al. (1993). Characterization of antinuclear autoantibodies present in the serum from nonobese diabetic (NOD) mice. Clin Immunol Immunopathol68:350-356.
13.
Humphreys-Beher MG, Hu Y., Nakagawa Y., Wang P.-L, Purushotham KR (1994). Utilization of the non-obese diabetic (NOD) mouse as an animal model for the study of secondary Sjögren's syndrome. Adv Exp Med Biol350:631-636.
14.
Jonsson R.Holmdahl R. (1990). Infiltrating mononuclear cells in salivary glands and kidneys in autoimmune MRL/Mp-lpr/lpr mice express IL-2 receptor and produce interferon gamma. J Oral Pathol Med19:330-334.
15.
Jonsson R., Tarkowski R., Bäckman K., Holmdahl R., Klareskog L. (1987). Sialadenitis in the MRL-1 mouse: morphology and immunohistochemical characterization of resident and infiltrating cells. Immunology60:611-616.
16.
Jonsson R., Pitts A., Mestecky J., Koopman W. (1991). Local IgA and IgM rheumatoid factor production in autoimmune MRL/lpr mice. Autoimmunity10:7-14.
17.
Kessler HS (1968). A laboratory model for Sjögren's syndrome. Am J Pathol52:671-685.
18.
Kimura T., Suzuki K., Inada S., Hayashi A., Saito H., Miyai T., et al. (1994). Induction of autoimmune disease by graft-versus-host reaction across MHC class II difference: modification of the lesions in IL-6 transgenic mice. Clin Exp Immunol95:525-529.
19.
Sato EH, Ariga H., Sullivan DA (1992). Impact of androgen therapy in Sjögren's syndrome: hormonal influence on lymphocyte populations and la expression in lacrimal glands of MRL/Mp-lpr/lpr mice. Invest Ophthalmol Vis Sci33:2537-2545.
20.
Skarstein K., Holmdahl R., Johannessen AC, Jonsson R. (1994). Oligoclonality of T cells in salivary glands of autoimmune MRL/lpr mice. Immunology81:497-501.
21.
Strasser A., Whittingham S., Vaux DL, Bath ML, Adams JM, Cory S., et al. (1991). Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease. Proc Natl Acad Sci USA88 :8661-8665.
22.
Vendramini Aclm, Soo C., Sullivan DA (1991). Testosterone-induced suppression of autoimmune disease in lacrimal tissue of mouse model (NZB/NZW F1) of Sjögren's syndrome . Invest Ophthalmol Vis Sci32 :3002-3006.
23.
Wahren M., Skarstein K., Blange I., Jonsson R. (1994). MRL/lpr mice produce anti-Ro 52 kD antibodies-detection, analysis of specificity and site of production. Immunology83:9-15.
24.
Wolff A., Scott J., Woods K., Fox PC (1991). An investigation of parotid gland function in autoimmune disease prone mice of different age groups. J Oral Pathol Med20:486-489.
25.
Wu J., Zhou T., Zhang J., He J., Gause WC, Mountz JD (1994). Correction of accelerated autoimmune disease by early replacement of the mutated lpr gene with the normal fas apoptosis gene in the T cells of transgenic MRL-lpr/lpr mice. Proc Natl Acad Sci USA91:2344-2348.
