Cellular Distribution of Prion Protein

为了研究人/鼠嵌合蛋白在细胞中的分布及其异常转化机制，我们建立了人/鼠嵌合蛋白转基因小鼠。由于重组病毒蛋白的高表达水平，利用免疫组织化学技术很容易检测到转基因小鼠体内正常细胞形态的病毒蛋白。在中枢神经系统中，重组病毒蛋白存在于神经元的轴突终末部分。在大体器官中，我们在肾上腺髓质、奥尔巴赫神经丛、甲状腺C细胞、垂体前叶、外周神经以及心脏和骨骼肌的肌细胞中检测到重组病毒蛋白。通过与野生型小鼠的免疫组织化学分析，证实这些重组病毒蛋白阳性细胞为重组病毒蛋白阳性细胞。在胚胎状态的研究中，起源于神经脊的细胞在蛋白免疫标记中呈强阳性。在重组PrP阳性细胞中，我们在Western印迹分析中检测到不同的Prion蛋白的糖基化模式。在传递实验中，我们的动物模型被认为是一个对人类普恩病毒高度敏感的模型。然而，在除中枢神经系统以外的一般器官中，不可能检测到异常的普恩蛋白亚型。因此，在不久的将来，应该澄清一种器官特异性因子，将正常细胞形式转换为异常形式的普恩蛋白。

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.