Goldmann W, Hunter N, Smith G, Foster J, Hope J
Institute for Animal Health, AFRC and MRC Neuropathogenesis Unit, Edinburgh, U.K.
J Gen Virol. 1994 May;75 ( Pt 5):989-95. doi: 10.1099/0022-1317-75-5-989.
Man and sheep are the two species in which spongiform encephalopathies occur naturally, and in which there are recognized genetic components that predispose an individual person or sheep to clinical disease. In both species mutations/polymorphisms in the PrP gene have been linked to the incidence of natural disease, but only in sheep is it possible to investigate by deliberate exposure to infection whether these polymorphisms are directly correlated with survival time. Cheviot sheep of different PrP genotypes were challenged with one of two isolates of scrapie or an isolate of bovine spongiform encephalopathy and the survival time and incidence of disease were monitored. Genotype analysis showed that dimorphisms in codons 136 and 171 of the ovine PrP gene correlated with control of disease incidence and modulation of incubation time. Crucially, the functional effects of these domains of PrP were shown to alternate depending on the isolate of infecting agent.
人类和绵羊是自然发生海绵状脑病的两个物种，在这两个物种中，都存在公认的遗传成分，使个体人或绵羊易患临床疾病。在这两个物种中，PrP基因的突变/多态性都与自然疾病的发生率有关，但只有在绵羊中，才有可能通过故意接触感染来研究这些多态性是否与存活时间直接相关。用两种痒病分离株之一或牛海绵状脑病分离株对不同PrP基因型的切维厄特羊进行攻击，并监测存活时间和疾病发生率。基因型分析表明，绵羊PrP基因第136和171密码子的双态性与疾病发生率的控制和潜伏期的调节相关。至关重要的是，这些PrP结构域的功能效应显示会因感染因子的分离株而异。
