Table 1.
Key aspects of mouse models of Sjögren syndrome.
| Mouse model | Advantages | Disadvantages |
|---|---|---|
| (NZB/NZW)F1 | Sjögren phenotypea upon treatment with incomplete Freund’s adjuvant or polyI:C | Symptoms also similar to systemic lupus erythematosus |
| NOD and derivatives | Sjögren phenotype can be controlled via housing conditions | NOD mice have lymphocytic infiltrations of all glands, develop diabetes |
| Idd3 and Idd5 congenic BL6 and MHC Class II Ab transgenic NOD develop Sjögren phenotype but not diabetes MHC Class II I-Ak transgenic NOD develops thyroiditis but not diabetes | Low incidence of thyroiditis | |
| NOD.H2h4 develops Sjögren phenotype but not diabetes | Sexes differ in cytokine profile and symptom severity | |
| MLR/lpr | Lymphocytic infiltration of lacrimal and salivary glands | Lymphocytic infiltration of numerous other organs Lack loss of secretory function and M3R antibodies Defective Fas receptor causes early mortality |
| Id3 KO | Sjögren phenotype | Caucasians retain Id3 expression |
| Complete disease penetrance | Late onset in mice | |
| PI3K KO | Sjögren phenotype | May not lose glandular secretion |
| BAFF transgenic | With age, develop Sjögren phenotype | Symptoms also similar to systemic lupus erythematosus |
| Unique marginal zone B cell population in salivary glands | No autoantibodies | |
| STIM1&2 ablation | Lymphoproliferation enables study of lymphomas | Reduction in regulatory T cells |
| Lymphocytic infiltration of salivary glands | ||
| Immunization models | Knowledge of precise time of disease initiation BALB/c immunized with Ro develop Sjögren phenotype | Repeated immunization over 5 months, no symptoms for 4 months |
| NOD immunized with M3R antibodies decreases salivation | Hyposalivation is transient | |
| Immunization with carbonic anhydrase II increases lymphocytic foci in salivary glands | Role of carbonic anhydrase II in Sjögren syndrome questioned | |
| Cytokine overexpression models | Cytokines produced by infiltrating lymphocytes and salivary gland epithelial cells | Disease etiology may be different in model than humans |
| IL-14α transgenic develop Sjögren phenotype, salivary flow decreased and IgM deposits detectable prior to infiltration, develop B cell lymphomas | ||
| IL-12 transgenic develop Sjögren phenotype, thyroiditis, lung pathology, and increased acinar cell volume |
a
Sjögren phenotype defined as lymphocytic infiltration of lacrimal and/or salivary glands and decreased glandular secretion with autoantibody formation.