Transmissible Spongiforme Encephalopathy in non-human primate model after intraperitoneal sCJD-, vCJD-, and BSE-inoculation in the rhesus monkey (Macaca mulatta)

恒河猴（Macaca mulatta）腹腔内接种 sCJD、vCJD 和 BSE 后非人类灵长类动物模型中的传染性海绵状脑病

• 批准号: 5442913
• 负责人: Professor Dr. Franz-Josef Kaup
• 金额: --
• 依托单位: Deutsches Primatenzentrum GmbH - Leibniz-Institut für Primatenforschung (DPZ)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5442913?language=en
• 关键词: Transmissible; Spongiforme; Encephalopathy; non; human

...In our project aspects of organismic biology and molecular pathology are combined. Our rhesus monkeys represent an animal model to assess early changes of behaviour in a way that is not feasible in experimental rodent prion infection models. Health control is tight because of the excellent expertise on macaques of our in-house veterinarians and animal caretakers. For the first time, telemetry is used in a prion infection model as a means to assess circadian rhythm, activity (sleep/wake-cycles) and body core temperature. This experimental approach offers the possibility to document ablation or changes of activity and behaviour as early markers for the infection and progression of the diseases. Extensive preinoculation studies have been performed, i.e. a large data colllection based on video, telemetry and visual observation already exists. Current work includes establishing mRNA detection for the putative surrogate marker gene alpha-haemoglobin-stabilizing-protein (AHSP) by RT-PCR and realtime RT-PCR. An archive with collected blood and bolld components, skin biospy specimens and lymph node specimens has already been established for future transmission and infection studies (8. Appendages). The existing project(s) enable(s) us to rapidly react on actual developments and scientific insights in prion research such as collection of cells or tissues suspected to play a role in replication and propagation of prions. Although we have a limited number of animals some might be used for intervention expreiment as already suggested by A. Aguzzi and J. Collinge (PrP decoys and monoclonal antibodies, respectively). Even if animals stay in a subclinical stage application of any therapeutic intervention measure could be investigated. For instance, there is an upcoming controversial debate between leading groups as to the benefit of monoclonal antibodies by reducing endogenous PrP or to an induction of loss of function of cellular PrP as a factor of neuronal survival (recent reports during the winter meeting Growth and Death in the Nervous System in St. Moritz from March 24-28, 2004).

．..在我们的项目中，有机生物学和分子病理学相结合。我们的恒河猴代表了一种动物模型，以一种在实验性啮齿动物朊病毒感染模型中不可行的方式评估早期行为变化。健康控制是严格的，因为我们的内部兽医和动物饲养员对猕猴有出色的专业知识。首次将遥测技术用于朊病毒感染模型，作为评估昼夜节律、活动（睡眠/觉醒周期）和核心体温的手段。这种实验方法提供了记录消融或活动和行为变化作为感染和疾病进展的早期标记的可能性。已经进行了广泛的接种前研究，即基于视频、遥测和目视观察的大量数据收集已经存在。目前的工作包括通过RT-PCR和实时RT-PCR建立对推定的替代标记基因α -血红蛋白稳定蛋白（AHSP）的mRNA检测。已经建立了一个档案，包括收集的血液和血液成分、皮肤生物标本和淋巴结标本，用于未来的传播和感染研究。附件)。现有的项目使我们能够对朊病毒研究的实际发展和科学见解做出快速反应，例如收集怀疑在朊病毒复制和传播中起作用的细胞或组织。虽然我们的动物数量有限，但正如a . Aguzzi和J. Collinge已经建议的那样，一些动物可能用于干预实验（分别是PrP诱饵和单克隆抗体）。即使动物处于亚临床阶段，也可以研究任何治疗干预措施的应用。例如，关于单克隆抗体通过减少内源性PrP或诱导细胞PrP功能丧失作为神经元存活因素的益处，领导小组之间即将进行一场有争议的辩论（最近在2004年3月24日至28日在圣莫里茨举行的神经系统生长与死亡冬季会议上的报告）。