Establishment of animal model for Sjogren's syndrome in mutant mice

干燥综合征是一种人类自身免疫性疾病，其特征是弥漫性淋巴样细胞浸润于唾液腺和泪腺，导致分泌不足导致口干和眼干。虽然我们已经提出了一些诱导自身免疫性涎牙体的小鼠模型，但尚未建立适合人类干燥综合征的动物模型。我们在此建立了胸腺切除的NFS/sld突变小鼠舌下粘液细胞分化阻滞的干燥综合征动物模型。通过直接分析从nfs /sld自身免疫性涎腺炎患者唾液腺组织中获得的RNA，分析了体内局部细胞因子基因表达。除免疫组织化学分析外，还使用逆转录酶聚合酶链反应（RT-PCR）评估细胞因子基因的表达。在炎性病变发生前检测IL-1 β、肿瘤坏死因子（TNF）的表达。此外，IL-2、IL-4和IL-6 mRNA在唾液腺中的过表达与典型的自身免疫性涎腺炎的发病明显一致，并随着年龄的增长而上调。这些结果表明，这些细胞因子基因的过表达在NFS/sld小鼠唾液腺器官定位自身免疫的发生和进展中起重要作用。

Sjogren's syndrome in humans is an autoimmune disease characterized by diffuse lymphoid cell infiltrates in the salivary and lacrimal glands, resulting in symptoms of dry mouth and dry eye due to insufficient secretion. Although we have proposed some murine models inducing autoimmune sialadentits, there has not been an established appropriate animal model specific for sjogren' syndrome in humans. We have here established an animal model for Sjogren's syndrome in thymectomezed NFS/sld mutant mice bearing sublingual mucous cell differentiation arrest. Local cytokine gene expression in vivo has been analyzed by direct analysis of RNA obtained from the salivary gland tissues inNFS/sld autoimmune sialadenitis. The expression of cytokine genes was assessed using reverse transcriptase polymerase chain reaction (RT-PCR), in addition to the immunohistochemical analysis. Expression of IL-1 beta, tumor necrosis factor(TNF) was detected before the onset of inflammatory lesions. Furthermore, IL-2, IL-4, and IL-6 mRNA overexpression in the salivary glands was clearly found in accordance with the onset of typical autoimmune sialadenitis, and was upregulated with advancing age. These results indicate that overexpression of these cytokine genes play an important role on the development and progression of organ-localized autoimmunity in the salivary gland in NFS/sld mice.