NEURON-SPECIFIC EXPRESSION OF A HAMSTER PRION PROTEIN MINIGENE IN TRANSGENIC MICE INDUCES SUSCEPTIBILITY TO HAMSTER SCRAPIE AGENT
NEURON-SPECIFIC EXPRESSION OF A HAMSTER PRION PROTEIN MINIGENE IN TRANSGENIC MICE INDUCES SUSCEPTIBILITY TO HAMSTER SCRAPIE AGENT
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DOI：
10.1016/0896-6273(95)90105-1
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发表时间：
1995-11-01
期刊：
影响因子：
16.2
通讯作者：
OLDSTONE, MBA
中科院分区：
文献类型：
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作者：
RACE, RE;PRIOLA, SA;OLDSTONE, MBA
为了研究细胞类型限制的仓鼠PrP表达对仓鼠瘙痒症因子的易感性的影响，我们使用含有在神经元特异性烯醇化酶启动子控制下的0.76 kb HPrP开放阅读框架的1 kb仓鼠cDNA克隆产生转基因小鼠。在这些小鼠中，仅在脑组织中检测到HPrP的表达，在小脑、海马、丘脑和大脑皮层的神经元中发现最高水平。这些转基因小鼠易受263K株仓鼠瘙痒病的感染，平均潜伏期为93天，而正常仓鼠为72天。相比之下，非转基因小鼠对这种药物不敏感。这些结果表明，神经元特异性表达的1 kb的HPrP小基因，包括HPrP开放阅读框是足以介导的易感性仓鼠瘙痒症，和非神经元脑细胞中的HPrP表达是没有必要克服TSE物种障碍。
To study the effect of cell type-restricted hamster PrP expression on susceptibility to the hamster scrapie agent, we generated transgenic mice using al 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.