REPLICATION OF DISTINCT SCRAPIE PRION ISOLATES IS REGION SPECIFIC IN BRAINS OF TRANSGENIC MICE AND HAMSTERS
REPLICATION OF DISTINCT SCRAPIE PRION ISOLATES IS REGION SPECIFIC IN BRAINS OF TRANSGENIC MICE AND HAMSTERS
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DOI：
10.1101/gad.6.7.1213
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发表时间：
1992-07-01
影响因子：
10.5
通讯作者：
PRUSINER, SB
中科院分区：
文献类型：
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作者：
HECKER, R;TARABOULOS, A;PRUSINER, SB
如果不是完全由PrP(SC)分子组成，那么PrP(SC)分子也是主要的组成。Prion分离株Sc237和139H在叙利亚、亚美尼亚和中国仓鼠以及表达叙利亚仓鼠PrP(SHaPrP)的转基因(TG)81小鼠中表现出明显不同的孵化时间。将转基因小鼠或中国仓鼠的普恩病毒重新传给叙利亚仓鼠，结果显示，这些普恩病毒分离株的原始特性得到了保留。当叙利亚仓鼠第一次接种139H普恩病毒，然后用Sc237普恩病毒攻击时，潜伏期由速度较快的Sc237分离株确定。区域定位研究表明，PrP(SC)在叙利亚仓鼠和TG(SHaPrP)7小鼠的脑中对Sc237和139H蛋白的积累具有不同的动力学和模式。不同的Prion分离株在大脑中诱导不同区域特异性PrP(SC)的积累，这为分离株的繁殖提供了一种新的机制，通过这种机制，它们可以在特定的神经元组中复制。通过PrP(SC)的不同构象、PrP(SC)的翻译后修饰(如天冬氨酸连接的糖基化)或Prion中尚未检测到的与PrP(SC)络合的大分子，Prion分离株可以靶向特定的CNS细胞。
Scrapie prions are composed largely, if not entirely, of PrP(Sc) molecules. The prion isolates Sc237 and 139H exhibit markedly different incubation times in Syrian, Armenian, and Chinese hamsters, as well as in transgenic (Tg) 81 mice expressing Syrian hamster PrP (SHaPrP). Repassage of prions from transgenic mice or Chinese hamsters into Syrian hamsters revealed that the original properties of the prion isolates are retained. When Syrian hamsters were first inoculated with 139H prions and subsequently challenged with Sc237 prions, the incubation period was determined by the faster Sc237 isolate. Regional mapping studies demonstrated different kinetics and patterns of PrP(Sc) accumulation for Sc237 and 139H prions in the brains of Syrian hamsters as well as Tg(SHaPrP)7 mice. That distinct prion isolates induce different region-specific accumulations of PrP(Sc) in brain suggests a novel mechanism for propagation of isolates whereby they replicate in particular sets of neurons. The prion isolates could be targeted to specific CNS cells by differing conformations of PrP(Sc), post-translational modifications of PrP(Sc) such as Asn-linked glycosylation, or an as yet undetected macromolecule complexed with PrP(Sc) in the prion.