MURINE TRANSGENIC MODELS OF PRION DISEASES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 Prion病，包括CreutzFeldt-Jakob病和库鲁病，是一种致命的神经退行性疾病，由于欧洲和美国出现了疯牛病，并有可能传播给人类，因此现在具有重要的医学意义。这些疾病也引起了巨大的科学兴趣，因为它们涉及一种全新的生物信息传输机制：它们是由内源性膜糖蛋白(PrPC)的构象变化引起的，PrPC将其转化为致病亚型(PrPSc)，在完全没有核酸的情况下具有传染性。哈里斯实验室对在细胞和分子水平上了解普恩病毒疾病很感兴趣。他们正在调查一些相互关联的问题，包括：PrPC如何转换为PrPSc？这些表单在单元格中是如何处理和定位的？它们还与哪些其他蛋白质相互作用？PrPC的正常功能是什么？PrP是如何杀死细胞的？PrP的作用形式是什么？为了解决这些问题，他们利用了几个实验系统，包括酵母、培养的哺乳动物细胞和转基因小鼠。我们采用了广泛的技术，包括细胞标记、蛋白质化学、显微镜、DNA微阵列分析、小鼠遗传学、神经病理学、动物生物测定和质谱学。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Prion diseases, including Creutzfeldt-Jakob disease and kuru, are fatal neurodegenerative disorders that are now of great medical importance because of emergence of "mad cow disease" in Europe and the U.S., and its likely transmission to human beings. These diseases are also of enormous scientific interest because they involve an entirely novel mechanism of biological information transfer: they result from a change in the conformation of an endogenous membrane glycoprotein (PrPC) which converts it into a pathogenic isoform (PrPSc) that is infectious in the complete absence of nucleic acid. The Harris laboratory is interested in understanding prion diseases at the cellular and molecular levels. They are investigating a number of interrelated questions, including: How is PrPC is converted into PrPSc? How are these forms processed and targeted in cells? What other proteins do they interact with? What is the normal function of PrPC? How do prions kill cells, and what forms of PrP are responsible? To address these issues, they utilize several experimental systems including yeast, cultured mammalian cells, and transgenic mice. We employ a wide range of techniques, including cell labeling, protein chemistry, microscopy, DNA microarray analysis, mouse genetics, neuropathology, animal bioassays, and mass spectrometry.