MURINE TRANSGENIC MODELS OF PRION DISEASES

朊病毒疾病的小鼠转基因模型

• 批准号: 7721483
• 负责人: DAVID A HARRIS
• 金额: $ 0.05万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721483
• 关键词: Address; Animals; Biological; Biological Assay; Bovine Spongiform Encephalopathy; Cells; Computer Retrieval of Information on Scientific Projects Database; Creutzfeldt-Jakob Syndrome; DNA Microarray Chip; DNA Microarray format; Disease; Europe; Funding; Genetic; Grant; Human; Institution; Kuru; Label; Laboratories; Mammalian Cell; Mass Spectrum Analysis; Medical; Membrane Glycoproteins; Microarray Analysis; Microscopy; Molecular; Molecular Conformation; Mus; Neurodegenerative Disorders; Nucleic Acids; Numbers; PrPC function; PrPSc Proteins; Prion Diseases; Prions; Process; Protein Chemistry; Proteins; Range; Research; Research Personnel; Resources; Source; System; Techniques; Transgenic Mice; Transgenic Model; United States National Institutes of Health; Yeasts; cell killing; interest; neuropathology; novel; pathogenic isoform; transmission process

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 朊病毒病，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”，并且很可能传播给人类，因此这些疾病现在具有重要的医学意义。这些疾病也具有巨大的科学意义，因为它们涉及一种全新的生物信息传递机制：它们是由内源性膜糖蛋白（PrPC）的构象变化引起的，这种变化将其转化为在完全没有核酸的情况下具有传染性的致病亚型（PrPSc）。 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 是如何转化为 PrPSc 的？这些形式在细胞中是如何被处理和定位的？它们与哪些其他蛋白质相互作用？ PrPC的正常功能是什么？朊病毒如何杀死细胞？朊病毒的哪种形式负责？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。我们采用多种技术，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。