A NOVEL NOD-DERIVED MURINE MODEL OF PRIMARY SJOGRENS-SYNDROME

Objective. The appearance of autoimmune diabetes Drier to autoimmune e xocrinopathy in the NOD mouse suggests that it is an excellent model o f secondary, but not primary, autoimmune sicca complications. Since th e unique major histocompatibility complex (MHC) I-A(g7) expression in NOD mice is essential for the development of insulitis and diabetes in these animals, we investigated exocrine gland function in NOD.B10.H2( b) mice, which have an MHC congenic to NOD, as a potential model for p rimary Sjogren's syndrome (SS). Methods. Histopathologic manifestation s of lymphocytic infiltrates into the pancreas and exocrine tissues we re examined by light microscopy. Sera were evaluated for the presence of antinuclear antibodies. Saliva, tears, and gland lysates were evalu ated for total volume and protein concentration, the aberrant expressi on and processing of parotid secretory protein, and cysteine protease activity. Results. NOD.B10.H2(b) mice exhibited the exocrine gland lym phocytic infiltration typical of the SS-like disease and dysfunction o bserved in NOD mice, but without the insulitis and diabetes, These mic e additionally expressed elevated levels of cysteine protease activity (a measure of apoptotic activity) and abnormal expression and cleavag e of parotid secretory protein in the submandibular tissues. Conclusio n. The results of this study suggest that the unique NOD MHC I-A(g7) i s not essential for exocrine tissue autoimmunity. Furthermore, the fin dings indicate that sicca syndrome occurs independently of auto-immune diabetes and that the congenic NOD.B10.H2(b) mouse represents a novel murine model of primary SS.