Cellular Distribution of Prion Protein

为了研究朊病毒蛋白的细胞分布和异常转化机制，我们建立了人/鼠嵌合朊病毒蛋白转基因小鼠。由于重组朊蛋白在转基因小鼠中的高表达，免疫组化技术可以很容易地检测到正常细胞形态的朊蛋白。在中枢神经系统中，重组朊蛋白在神经元的轴突末端被识别。在一般器官中，我们在肾上腺髓质、奥尔巴赫神经丛、甲状腺C细胞、脑垂体前叶、周围神经以及心脏和骨骼肌的肌细胞中检测到重组朊病毒蛋白。通过对野生型小鼠的免疫组化分析，证实重组朊蛋白阳性细胞为纯朊蛋白阳性细胞。在胚胎状态的研究中，来自神经嵴的细胞在朊蛋白免疫标记上呈强阳性。在重组朊蛋白阳性细胞中，Western blot检测到朊蛋白的不同糖基化模式。在传播实验中，我们的动物模型被认为是对人类朊病毒高度敏感的模型。然而，除了中枢神经系统外，一般器官中不可能检测到异常的朊病毒蛋白异构体。因此，在不久的将来，将正常细胞形式转化为异常形式的朊病毒蛋白的器官特异性因子应该得到澄清。

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.