转基因研究表明，在羊瘙痒病朊病毒复制过程中，同源朊蛋白异构体之间存在相互作用。
Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication.
作者信息
Prusiner S B, Scott M, Foster D, Pan K M, Groth D, Mirenda C, Torchia M, Yang S L, Serban D, Carlson G A
机构信息
Department of Neurology, University of California, San Francisco 94143.
出版信息
Cell. 1990 Nov 16;63(4):673-86. doi: 10.1016/0092-8674(90)90134-z.
Transgenic (Tg) mice expressing both Syrian hamster (Ha) and mouse (Mo) prion protein (PrP) genes were used to probe the mechanism of scrapie prion replication. Four Tg lines expressing HaPrP exhibited distinct incubation times ranging from 48 to 277 days, which correlated inversely with HaPrP mRNA and HaPrPC. Bioassays of Tg brain extracts showed that the prion inoculum dictates which prions are synthesized de novo. Tg mice inoculated with Ha prions had approximately 10(9) ID50 units of Ha prions per gram of brain and less than 10 units of Mo prions. Conversely, Tg mice inoculated with Mo prions synthesized Mo prions but not Ha prions. Similarly, Tg mice inoculated with Ha prions exhibited neuropathologic changes characteristic of hamsters with scrapie, while Mo prions produced changes similar to those in non-Tg mice. Our results argue that species specificity of scrapie prions resides in the PrP sequence and prion synthesis is initiated by a species-specific interaction between PrPSc in the inoculum and homologous PrPC.
利用同时表达叙利亚仓鼠（Ha）和小鼠（Mo）朊病毒蛋白（PrP）基因的转基因（Tg）小鼠来探究羊瘙痒病朊病毒复制的机制。四个表达HaPrP的Tg品系表现出不同的潜伏期，从48天到277天不等，这与HaPrP mRNA和HaPrPC呈负相关。对Tg脑提取物的生物测定表明，朊病毒接种物决定了哪些朊病毒是从头合成的。接种Ha朊病毒的Tg小鼠每克脑中约有10^9个半数感染剂量（ID50）单位的Ha朊病毒，而Mo朊病毒不到10个单位。相反，接种Mo朊病毒的Tg小鼠合成Mo朊病毒但不合成Ha朊病毒。同样，接种Ha朊病毒的Tg小鼠表现出具有羊瘙痒病的仓鼠特有的神经病理变化，而Mo朊病毒产生的变化与非Tg小鼠相似。我们的结果表明，羊瘙痒病朊病毒的物种特异性存在于PrP序列中，并且朊病毒合成是由接种物中的PrPSc与同源PrPC之间的物种特异性相互作用引发的。
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