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Cellular Distribution of Prion Protein

朊病毒蛋白的细胞分布

基本信息

批准号：
10480211
负责人：
KITAMOTO Tetsuyuki
金额：
$ 8.38万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10480211/
关键词：
prion protein cellular distribution conversion mechanism transgenic mice embryology organ-specific factor

项目摘要

To study the cellular distribution and the mechanism of abnormal conversion of prion protein, we established the transgenic mice with human/mouse chimeric prion protein. Normal cellular form of prion protein in the transgenic mice was easily detected by the immunohistochemical techniques because of high expression level of recombinant prion protein. In the central nervous system, recombinant prion protein was recognized in the axon terminal portion of the neurons. In general organs, we detected recombinant prion protein in the adrenal medulla, the Auerbach's plexus, C cells of the thyroid gland, the anterior pituitary gland, the peripheral nerves, and the myocytes in the heart and the skeletal muscles. We confirmed these recombinant prion protein positive cells were rally prion protein-positive cells in the immunohistochemical analysis with the wild-type mice. In the study of the embryonic state, the cells originated from the neural crest were strongly positive in the prion protein immunolabellings. Among recombinant prion protein-positive cells, we detected the different glycosylation-pattern of prion protein in the Western blot analysis. In the transmission experiment, our animal model was recognized to be a highly sensitive model for human prions. However, it is not possible to detect abnormal isoform of prion protein in general organs except for the central nervous system. Thus, an organ-specific factor to convert the normal cellular form into the abnormal form of prion protein should be clarified in near future.

为了研究朊蛋白的细胞分布及其异常转化机制，我们建立了人/鼠嵌合朊蛋白转基因小鼠。由于重组朊蛋白在转基因小鼠中的高表达水平，免疫组化技术很容易检测到正常细胞形式的朊蛋白。在中枢神经系统中，重组朊病毒蛋白在神经元的轴突末端部分被识别。在一般器官中，我们在肾上腺髓质、奥尔巴赫氏神经丛、甲状腺C细胞、垂体前叶、周围神经以及心脏和骨骼肌中的肌细胞中检测到重组朊蛋白。用野生型小鼠进行免疫组化分析，证实这些重组朊蛋白阳性细胞是重组朊蛋白阳性细胞。在胚胎状态的研究中，神经嵴来源的细胞在朊蛋白免疫标记中呈强阳性。在重组朊蛋白阳性细胞中，我们用Western印迹分析检测到朊蛋白不同的糖基化模式。在传播实验中，我们的动物模型被认为是对人朊病毒高度敏感的模型。然而，在除中枢神经系统外的一般器官中不可能检测到朊病毒蛋白的异常同种型。因此，在不久的将来，一个器官特异性的因素，正常的细胞形式转换为异常形式的朊病毒蛋白应澄清。