E2f1-deficient NOD/SCID mice have dry mouth due to a change of acinar/duct structure and the down-regulation of AQP5 in the salivary gland
E2f1-deficient NOD/SCID mice have dry mouth due to a change of acinar/duct structure and the down-regulation of AQP5 in the salivary gland
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DOI：
10.1007/s00424-012-1183-y
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发表时间：
2013-02-01
影响因子：
4.5
通讯作者：
Sugiya, Hiroshi
中科院分区：
文献类型：
--
作者：
Satoh, Keitaro;Narita, Takanori;Sugiya, Hiroshi
非肥胖糖尿病（NOD）小鼠已被用作口干的模型。NOD小鼠缺乏E2 f1（一种转录因子）编码基因，与对照NOD小鼠相比，其唾液分泌减少的进展速度更快。然而，模型小鼠与潜在疾病如糖尿病有关。我们现在已经建立了E2 f1缺陷型NOD/严重联合免疫缺陷病（NOD/SCID.E2f1（-/-））小鼠，以避免糖尿病的发生（Matsui-Inohara等人，Exp Biol Med（Maywood）234（12）：1525-1536，2009）。在这项研究中，我们研究了NOD/SCID.E2f1（-/-）小鼠口干的病理生理学特征。在NOD/SCID.E2f1（-/-）小鼠中，用毛果芸香碱刺激的分泌唾液的体积约为对照NOD/SCID小鼠的三分之一。在行为分析中，NOD/SCID. E2 f1（-/-）小鼠在进食干食物时大量饮水，饮水频率和时间几乎是对照NOD/SCID小鼠的两倍。苏木精-伊红染色的下颌下腺组织学分析显示，NOD/SCID. E2 f1（-/-）小鼠比NOD/SCID小鼠具有更多的导管。免疫印迹分析显示，NOD/SCID. E2 f1（-/-）小鼠腮腺和颌下腺中腺泡细胞标志物水通道蛋白5（AQP 5）的表达低于NOD/SCID小鼠。免疫组织化学分析显示，NOD/SCID. E2 f1（-/-）小鼠的腮腺腺泡和下颌下腺泡中AQP 5的定位与NOD/SCID小鼠不同，NOD/SCID. E2 f1（-/-）小鼠的AQP 5从顶膜向胞浆呈弥漫性定位。在NOD/SCID.E2f1（-/-）小鼠的下颌下腺中检测到AQP 5的泛素化。提示NOD/SCID.E2f1（-/-）小鼠唾液腺腺泡/导管结构的改变和AQP 5表达下调是导致唾液分泌减少的原因。
Non-obese diabetic (NOD) mice have been used as a model for dry mouth. NOD mice lacking the gene encoding E2f1, a transcription factor, develop hyposalivation more rapidly progressively than control NOD mice. However, the model mice are associated with an underlying disease such as diabetes. We have now established E2f1-deficient NOD/severe combined immunodeficiency disease (NOD/SCID.E2f1(-/-)) mice to avoid the development of diabetes (Matsui-Inohara et al., Exp Biol Med (Maywood) 234(12):1525-1536, 2009). In this study, we investigated the pathophysiological features of dry mouth using NOD/SCID.E2f1(-/-) mice. In NOD/SCID.E2f1(-/-) mice, the volume of secreted saliva stimulated with pilocarpine is about one third that of control NOD/SCID mice. In behavioral analysis, NOD/SCID.E2f1(-/-) mice drank plenty of water when they ate dry food, and the frequency and time of water intake were almost double compared with control NOD/SCID mice. Histological analysis of submandibular glands with hematoxylin-eosin stain revealed that NOD/SCID.E2f1(-/-) mice have more ducts than NOD/SCID mice. In western blot analysis, the expression of aquaporin 5 (AQP5), a marker of acinar cells, in parotid and in submandibular glands of NOD/SCID.E2f1(-/-) mice was lower than in NOD/SCID mice. Immunohistochemical analysis of parotid and submandibular acini revealed that the localization of AQP5 in NOD/SCID.E2f1(-/-) mice differs from that in NOD/SCID mice; AQP5 was leaky and diffusively localized from the apical membrane to the cytosol in NOD/SCID.E2f1(-/-) mice. The ubiquitination of AQP5 was detected in submandibular glands of NOD/SCID.E2f1(-/-) mice. These findings suggest that the change of acinar/duct structure and the down-regulation of AQP5 in the salivary gland cause the pathogenesis of hyposalivation in NOD/SCID.E2f1(-/-) mice.