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鉴定两个可改变羊瘙痒病潜伏期的朊病毒蛋白区域。

Identification of two prion protein regions that modify scrapie incubation time.

作者信息

Supattapone S, Muramoto T, Legname G, Mehlhorn I, Cohen F E, DeArmond S J, Prusiner S B, Scott M R

机构信息

Institute for Neurodegenerative Diseases, University of California, San Francisco, California 94143, USA.

出版信息

J Virol. 2001 Feb;75(3):1408-13. doi: 10.1128/JVI.75.3.1408-1413.2001.

Abstract

A series of prion transmission experiments was performed in transgenic (Tg) mice expressing either wild-type, chimeric, or truncated prion protein (PrP) molecules. Following inoculation with Rocky Mountain Laboratory (RML) murine prions, scrapie incubation times for Tg(MoPrP)4053, Tg(MHM2)294/Prnp(0/0), and Tg(MoPrP, Delta23-88)9949/Prnp(0/0) mice were approximately 50, 120, and 160 days, respectively. Similar scrapie incubation times were obtained after inoculation of these lines of Tg mice with either MHM2(MHM2(RML)) or MoPrP(Delta23-88)(RML) prions, excluding the possibility that sequence-dependent transmission barriers could account for the observed differences. Tg(MHM2)294/Prnp(0/0) mice displayed prolonged scrapie incubation times with four different strains of murine prions. These data provide evidence that the N terminus of MoPrP and the chimeric region of MHM2 PrP (residues 108 through 111) both influence the inherent efficiency of prion propagation.

摘要

在表达野生型、嵌合型或截短型朊病毒蛋白(PrP)分子的转基因(Tg)小鼠中进行了一系列朊病毒传播实验。在用落基山实验室(RML)鼠朊病毒接种后,Tg(MoPrP)4053、Tg(MHM2)294/Prnp(0/0)和Tg(MoPrP, Delta23 - 88)9949/Prnp(0/0)小鼠的瘙痒病潜伏期分别约为50天、120天和160天。用MHM2(MHM2(RML))或MoPrP(Delta23 - 88)(RML)朊病毒接种这些品系的Tg小鼠后,获得了相似的瘙痒病潜伏期,排除了序列依赖性传播障碍可解释观察到的差异的可能性。Tg(MHM2)294/Prnp(0/0)小鼠在感染四种不同鼠朊病毒株时显示出延长的瘙痒病潜伏期。这些数据提供了证据,表明MoPrP的N末端和MHM2 PrP的嵌合区域(第108至111位氨基酸残基)均影响朊病毒繁殖的固有效率。

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