Biology of Prion Protein and the TSE Diseases

朊蛋白的表达是朊病毒感染和疾病所必需的，但个体细胞类型在不同感染器官中的作用尚不清楚。为了解决这个问题，我们使用了仅在神经元或多种细胞类型中表达PrP的转基因小鼠。在多种细胞类型表达PrP的小鼠眼内接种瘙痒病后，我们注意到视网膜细胞变性和视网膜小胶质细胞活化。在仅在神经元中表达PrP的小鼠中，未发现视网膜变性或小胶质细胞活化，从而检测到PrP异常。这种差异在两种小鼠品系的脑组织中没有观察到，脑组织的激活和退化都很广泛。提示瘙痒病感染后视网膜和脑内小胶质细胞的激活机制不同，视网膜小胶质细胞表达PrP可能是这一过程中的重要因素。

Prion protein expression is required for prion infection and disease, but the roles of individual cell types in different infected organs is not yet clear. To approach this problem we have used transgenic mice expressing PrP in neurons only or in multiple cell types. After intraocular scrapie inoculation in mice expressing PrP in multiple cell types we noted degeneration of retinal cells and retinal microglial activation. In mice expressing PrP in neurons only, abnormal PrPres was detected by there was no retinal degeneration or microglial activation. This difference was not seen in brain tissue where activation and degeneration were extensive in both mouse strains. These results suggest that different microglial activation mechanisms occur after scrapie infection in retina and brain, and that PrP expression by retinal microglia might be an important factor in this process. Transgenic mice expressing two different alleles of deer prion protein were generated. Mice with the G96 allele were found to be susceptible to disease induced by 4 different pools of wild type CWD agent from deer or elk. In contrast S96 mice were resistant to all these pools. Since deer with the S96 allele are partially resistant to CWD it is possible that only a small number of CWD strain can infect such deer. Alternatively S96 deer might have other mechanisms of resistance to all strains of CWD. We are currently trying to distinguish between these possibilities by inoculating our mice with CWD agent derived from infected S96 deer.