Race R E, Priola S A, Bessen R A, Ernst D, Dockter J, Rall G F, Mucke L, Chesebro B, Oldstone M B
Laboratory of Persistent Viral Diseases, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840, USA.
Neuron. 1995 Nov;15(5):1183-91. doi: 10.1016/0896-6273(95)90105-1.
To study the effect of cell type-restricted hamster PrP expression on susceptibility to the hamster scrapie agent, we generated transgenic mice using a 1 kb hamster cDNA clone containing the 0.76 kb HPrP open reading frame under control of the neuron-specific enolase promoter. In these mice, expression of HPrP was detected only in brain tissue, with highest levels found in neurons of the cerebellum, hippocampus, thalamus, and cerebral cortex. These transgenic mice were susceptible to infection by the 263K strain of hamster scrapie with an average incubation period of 93 days, compared to 72 days in normal hamsters. In contrast, nontransgenic mice were not susceptible to this agent. These results indicate that neuron-specific expression of the 1 kb HPrP minigene including the HPrP open-reading frame is sufficient to mediate susceptibility to hamster scrapie, and that HPrP expression in nonneuronal brain cells is not necessary to overcome the TSE species barrier.
为研究细胞类型限制的仓鼠朊蛋白（PrP）表达对仓鼠瘙痒病病原体易感性的影响，我们使用了一个1 kb的仓鼠cDNA克隆构建转基因小鼠，该克隆包含在神经元特异性烯醇化酶启动子控制下的0.76 kb仓鼠PrP（HPrP）开放阅读框。在这些小鼠中，仅在脑组织中检测到HPrP的表达，在小脑、海马体、丘脑和大脑皮层的神经元中表达水平最高。这些转基因小鼠对仓鼠瘙痒病263K毒株感染敏感，平均潜伏期为93天，而正常仓鼠为72天。相比之下，非转基因小鼠对该病原体不敏感。这些结果表明，包含HPrP开放阅读框的1 kb HPrP小基因在神经元中的特异性表达足以介导对仓鼠瘙痒病的易感性，并且非神经元脑细胞中的HPrP表达对于跨越传染性海绵状脑病（TSE）种间屏障并非必需。
