University of Cambridge, Department of Veterinary Medicine, Madingley Road, Cambridge, CB3 OES, UK.
Exp Mol Pathol. 2012 Feb;92(1):167-74. doi: 10.1016/j.yexmp.2011.11.004. Epub 2011 Nov 19.
Ovine prion strains have typically been identified by their transmission properties, which include incubation time and lesion profile, in wild type mice. The existence of scrapie isolates that do not propagate in wild type mice, defined here as "poor" transmitters, are problematic for conventional prion strain typing studies as no incubation time or neuropathology can be recorded. This may arise because of the presence of an ovine prion strain within the original inoculum that does not normally cross the species barrier into wild type mice or the presence of a low dose of an infectious ovine prion strain that does. Here we have used tg59 and tg338 mouse lines, which are transgenic for ovine ARQ or VRQ PrP, respectively, to strain type "poor" transmitter ovine scrapie isolates. ARQ and VRQ homozygous "poor" transmitter scrapie isolates were successfully propagated in both ovine PrP transgenic mouse lines. We have used secondary passage incubation time, PrPSc immunohistochemistry and molecular profile, to show that different prion strains can be isolated from different "poor" transmitter samples during serial passage in ovine PrP transgenic mice. Our observations show that poor or inadequate transmissibility of some classical scrapie isolates in wild type mice is associated with unique ovine prion strains in these particular sheep scrapie samples. In addition, the analysis of the scrapie isolates used here revealed that the tg338 mouse line was more versatile and more robust at strain typing ovine prions than tg59 mice. These novel observations in ovine PrP transgenic mice highlight a new approach to ovine prion strain typing.
绵羊朊病毒株通常通过其在野生型小鼠中的传播特性来鉴定，包括潜伏期和病变谱。这里定义的不会在野生型小鼠中传播的瘙痒病分离株（“不良”传播者）的存在，对常规朊病毒株分型研究构成了问题，因为无法记录潜伏期或神经病理学。这可能是由于原始接种物中存在通常不会跨越物种屏障进入野生型小鼠的绵羊朊病毒株，或者存在低剂量的可感染绵羊朊病毒株。在这里，我们使用了 tg59 和 tg338 小鼠系，它们分别为绵羊 ARQ 或 VRQ PrP 的转基因，用于对“不良”传播者绵羊瘙痒病分离株进行株型分型。ARQ 和 VRQ 纯合“不良”传播者瘙痒病分离株在两种绵羊 PrP 转基因小鼠系中均成功繁殖。我们使用次级传代潜伏期、PrPSc 免疫组织化学和分子谱，表明在绵羊 PrP 转基因小鼠的连续传代中，可以从不同的“不良”传播者样本中分离出不同的朊病毒株。我们的观察表明，一些经典瘙痒病分离株在野生型小鼠中的不良或不足的传染性与这些特定绵羊瘙痒病样本中的独特绵羊朊病毒株有关。此外，对这里使用的瘙痒病分离株的分析表明，与 tg59 小鼠相比，tg338 小鼠系在绵羊朊病毒株的分型方面更通用且更稳健。这些在绵羊 PrP 转基因小鼠中的新观察结果强调了一种绵羊朊病毒株分型的新方法。
