E2F-1-Deficient NOD/SCID Mice Developed Showing Decreased Saliva Production
E2F-1-Deficient NOD/SCID Mice Developed Showing Decreased Saliva Production
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DOI：
10.3181/0905-rm-173
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发表时间：
2009-12-01
影响因子：
3.2
通讯作者：
Senpuku, Hidenobu
中科院分区：
文献类型：
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作者：
Matsui-Inohara, Hikaru;Uematsu, Hiroshi;Senpuku, Hidenobu
非肥胖糖尿病小鼠（NOD）是研究胰岛素依赖型1型糖尿病（IDDM）和干燥综合征（SS）的最具特征的模型。在以前的报告中，我们发现NOD.E2f1（-/-）小鼠与NOD小鼠相比，表现出更大的向IDDM和SS的进展性发展。我们以前的数据表明，调节性T细胞（CD 4（+）CD 25（+））的进行性减少和全身胰岛素分泌系统的减少，唾液与IDDM和SS的进展有关。因此，为了确定E2 F-1缺陷型NOD小鼠中早发性IDDM SS的机制，需要通过产生T和B细胞不发育的E2 F-1缺陷型NOD/SCID小鼠进行进一步研究。本研究的目的是分析E2 F-1分子在IDDM和SS发生发展中的重要作用，以及NOD/SCID小鼠在NOD背景下的胰岛和唾液腺功能障碍。我们使用同源重组生产了NOD/SCID.E2f1（-/-）小鼠;确定糖尿病的发展;测量唾液和胰岛素的产生;并进行组织学分析。缺陷小鼠显示唾液体积减少;没有淋巴细胞浸润到唾液腺中;没有糖尿病的发展;并且在调节下颌下腺增殖和形态发生的唾液腺导管中没有FGFR-2b的蛋白定位。因此，我们认为E2 F-1的缺乏诱导调节性T细胞的减少和自身反应性T细胞的增加;然而，E2 F-1缺乏与胰腺β细胞在胰岛素分泌中的T和B细胞非依赖性功能障碍无关。此外，E2 F-1缺乏与唾液腺的T和B细胞非依赖性功能障碍有关，表现出唾液产生量的减少。我们认为E2 F-1也可能与导管外分泌细胞的分化有关，其中FGFR-2b在唾液腺中表达。E2 F-1缺陷型NOD/SCID小鼠模型可用于显示唾液腺的发育;也可用于人源化小鼠的各种实验。实验生物医学234：1525-1536，2009
The non-obese diabetic mouse (NOD) is the most characterized model used to study insulin-dependent type 1 diabetes mellitus (IDDM) and Sjogren's syndrome (SS). In a previous report, we found NOD.E2f1(-/-) mice show a greater progressive development to IDDM and SS compared to NOD mice. Our previous data indicated a progressive decrease in regulatory T cells (CD4(+)CD25(+)) and a decrease in the systemic secretion systems for insulin, and saliva was associated with the progression of IDDM and SS. Therefore, to define the mechanism of early-onset IDDM SS in E2F-1 deficient NOD mice required further investigation by producing E2F-1 deficient NOD/SCID mice in which the T and B cells do not develop. The purpose here was to analyze the essential function of the E2F-1 molecule in the development of IDDM and SS; and the dysfunction of the pancreas islet and salivary gland in the NOD background using NOD/SCID mice. We produced NOD/SCID.E2f1(-/-) mice using homologous recombination; determined diabetes development; measured saliva and insulin production; and performed a histological analysis. The deficient mice showed a decreasing volume of saliva; no infiltration of lymphocytes into salivary glands; no development of diabetes; and no protein localization of FGFR-2b in the ducts of the salivary gland that regulates submandibular gland proliferation and morphogenesis. Therefore, we considered a deficiency in E2F-1 induces a decrease in regulatory T cells and an increase in auto-reactive T cells; however, the E2F-1 deficiency is not associated with T and B cells-independent dysfunction of pancreatic p cell in insulin secretion. Further, the E2F-1 deficiency is associated with T and B cells-independent dysfunction of the salivary gland exhibits a decrease in saliva production volume. We suggest E2F-1 may be also associated with the differentiation of exocrine cells in the duct where FGFR-2b is expressed in the salivary gland. The E2F-1 deficient NOD/SCID mouse model is useful for showing the development of the salivary gland; and is also useful for various experiments in humanized mice. Exp Biol Med 234:1525-1536, 2009