MURINE TRANSGENIC MODELS OF PRION DISEASES

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 朊病毒疾病，包括克雅氏病和库鲁病，是致命的神经退行性疾病，由于欧洲和美国出现了"疯牛病"，以及它可能传染给人类。这些疾病也是巨大的科学兴趣，因为它们涉及一个全新的生物信息传递机制：它们是由内源性膜糖蛋白（PrPC）的构象变化，将其转化为致病性同种型（PrPSc），在完全没有核酸的情况下是传染性的。 哈里斯实验室有兴趣在细胞和分子水平上了解朊病毒疾病。他们正在研究一些相互关联的问题，包括：PrPC如何转化为PrPSc？这些形式是如何在细胞中加工和靶向的？它们还与哪些蛋白质相互作用？PrPC的正常功能是什么？朊病毒是如何杀死细胞的，什么形式的PrP负责？为了解决这些问题，他们利用了几种实验系统，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。

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.