Robinson C P, Yamachika S, Bounous D I, Brayer J, Jonsson R, Holmdahl R, Peck A B, Humphreys-Beher M G
University of Florida, Gainesville 32610, USA.
Arthritis Rheum. 1998 Jan;41(1):150-6. doi: 10.1002/1529-0131(199801)41:1<150::AID-ART18>3.0.CO;2-T.
The appearance of autoimmune diabetes prior to autoimmune exocrinopathy in the NOD mouse suggests that it is an excellent model of secondary, but not primary, autoimmune sicca complications. Since the 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.H2b mice, which have an MHC congenic to NOD, as a potential model for primary Sjögren's syndrome (SS).
Histopathologic manifestations of lymphocytic infiltrates into the pancreas and exocrine tissues were examined by light microscopy. Sera were evaluated for the presence of antinuclear antibodies. Saliva, tears, and gland lysates were evaluated for total volume and protein concentration, the aberrant expression and processing of parotid secretory protein, and cysteine protease activity.
NOD.B10.H2b mice exhibited the exocrine gland lymphocytic infiltration typical of the SS-like disease and dysfunction observed in NOD mice, but without the insulitis and diabetes. These mice additionally expressed elevated levels of cysteine protease activity (a measure of apoptotic activity) and abnormal expression and cleavage of parotid secretory protein in the submandibular tissues.
The results of this study suggest that the unique NOD MHC I-A(g7) is not essential for exocrine tissue autoimmunity. Furthermore, the findings indicate that sicca syndrome occurs independently of autoimmune diabetes and that the congenic NOD.B10.H2b mouse represents a novel murine model of primary SS.
非肥胖糖尿病（NOD）小鼠中自身免疫性糖尿病先于自身免疫性外分泌病出现，这表明它是继发性而非原发性自身免疫性干燥并发症的极佳模型。由于NOD小鼠中独特的主要组织相容性复合体（MHC）I-A(g7)表达对于这些动物发生胰岛炎和糖尿病至关重要，我们研究了NOD.B10.H2b小鼠的外分泌腺功能，该小鼠具有与NOD同基因的MHC，作为原发性干燥综合征（SS）的潜在模型。
通过光学显微镜检查淋巴细胞浸润胰腺和外分泌组织的组织病理学表现。评估血清中抗核抗体的存在情况。评估唾液、泪液和腺体裂解物的总体积和蛋白质浓度、腮腺分泌蛋白的异常表达和加工情况以及半胱氨酸蛋白酶活性。
NOD.B10.H2b小鼠表现出类似SS疾病典型的外分泌腺淋巴细胞浸润以及在NOD小鼠中观察到的功能障碍，但没有胰岛炎和糖尿病。这些小鼠还表现出半胱氨酸蛋白酶活性水平升高（凋亡活性的一种衡量指标）以及下颌下组织中腮腺分泌蛋白的异常表达和裂解。
本研究结果表明，独特性的NOD MHC I-A(g7)对于外分泌组织自身免疫并非必不可少。此外，研究结果表明干燥综合征独立于自身免疫性糖尿病发生，并且同基因的NOD.B10.H2b小鼠代表了一种新型的原发性SS小鼠模型。
