The non-obese diabetic (NOD) mouse model is the most widely described and validated method for investigating human primary Sjögren's syndrome (SS) and represents a useful model for translational studies. However, the systemic disease manifestation in NOD mice is sensitive to the housing environment, as stress modulates the immune system, so it is essential to confirm that readouts are robust, reproducible, and sensitive to known clinical treatments. This protocol describes the establishment of the spontaneous NOD model of SS and underscores the necessity of model validation to ensure that the housing environment is compatible. © 2019 by John Wiley & Sons, Inc.
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