Various animal models have been developed throughout the years for Sjögren’s syndrome, which elicit both spontaneous and experimentally induced disease development. The use of such animal models makes it possible to study different stages of disease development in a controlled environment, in addition to testing different therapeutic approaches. Mouse strains that naturally develop an immune condition resembling SS were first described in the late 1960s. Ideally, a model for SS should display the common symptoms of ocular and oral dryness, in addition to chronic inflammation in the lachrymal and salivary glands, and systemic immunological features that resemble the human form of the disease, such as antinuclear antibodies, autoantibodies and hypergammaglobulinemia.
Some of the best characterised animal models for studying Sjögren’s syndrome include the Murphy Roth’s Large (MRL/lpr) and the Non-obese Diabetic (NOD) mouse. To date, the NOD mouse is one of the most used and thus best described out of these models. However, the NOD model has also been applied to study insulin dependent diabetes mellitus. Nonetheless, due to the loss of secretory function alongside lymphocytic infiltration in its exocrine glands this model has also been widely used for studying Sjögren’s syndrome-like disease development. As the NOD mouse also develops diabetes, this model seems more appropriate for studying the secondary rather than primary form of Sjögren’s syndrome. To overcome this predicament another congenic NOD strain has been developed, namely the NOD.B10.H2b mouse. Here the NOD MHC I-Ag7 locus has been replaced with the non-diabetogenic MHC I-Ab locus of C57BL/10 mice. Hence, due to the lack of the diabetogenic locus this novel NOD.B10.H2b strain does not develop diabetes. Moreover, the NOD.B10.H2b mouse also exhibits all the immunopathological manifestations of the human form of primary Sjögren’s syndrome such as loss of secretory function, histological features with lymphocytic infiltration of exocrine glands (lacrimal and salivary glands), the presence of hypergammaglobulinaemia and the production of antinuclear autoantibodies. However, in contrast to human primary Sjögren’s syndrome, in NOD.B10.H2b mice anti-Ro/SSA and anti-La/SSB autoantibodies have not been detected, and there seems to be an equal distribution of disease development amongst both males and females.
Taking all the aforementioned features into account the different mouse models described have their strengths and limitations, yet nonetheless represent solid starting points for unraveling different aspects of disease development and pathogenesis.