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

在我们的项目中，有机生物学和分子病理学的各个方面被结合在一起。我们的恒河猴代表了一种评估早期行为变化的动物模型，这种方法在实验性啮齿动物普恩病毒感染模型中是不可行的。卫生控制是严格的，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。遥测技术首次被用在普恩病毒感染模型中，作为评估昼夜节律、活动(睡眠/清醒周期)和体温的一种手段。这一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志的可能性。已经进行了广泛的接种前研究，即已经存在基于视频、遥测和视觉观察的大量数据收集。目前的工作包括建立RT-PCR和Real-Time RT-PCR对可能的替代标记基因α-血红蛋白稳定蛋白(AHSP)的mRNA检测。收集的血液和胆汁成分、皮肤活检标本和淋巴结标本的档案已经建立，用于未来的传播和感染研究(8.附录)。现有的项目(S)使我们(S)能够对普恩研究的实际发展和科学见解做出快速反应，例如收集被怀疑在普恩复制和繁殖中发挥作用的细胞或组织。虽然我们的动物数量有限，但正如A.Aguzzi和J.Collinger(分别是PrP诱饵和单抗)所建议的那样，一些动物可能被用于干预实验。即使动物处于亚临床阶段，也可以对任何治疗干预措施的应用进行调查。例如，关于减少内源性PrP的单抗的益处或诱导作为神经元存活因素的细胞PrP的功能丧失的问题，领导小组之间即将进行一场有争议的辩论(最近的报告在2004年3月24-28日在圣莫里茨举行的神经系统生长和死亡冬季会议上)。

...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).