MICE DEVOID OF PRP ARE RESISTANT TO SCRAPIE
MICE DEVOID OF PRP ARE RESISTANT TO SCRAPIE
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DOI：
10.1016/0092-8674(93)90360-3
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发表时间：
1993-07-02
期刊：
影响因子：
64.5
通讯作者：
WEISSMANN, C
中科院分区：
文献类型：
--
作者：
BUELER, H;AGUZZI, A;WEISSMANN, C
S.B.Prusiner提出，瘙痒病的感染源是PrP(SC)，它是正常宿主蛋白PrP(C)的修饰形式。PrP(C)缺失的PRN-P0/0小鼠表现出正常的发育和行为。当接种小鼠痒疹病毒时，它们至少在13个月内没有瘙痒症状，而野生型对照组在6个月内全部死亡。令人惊讶的是，杂合的PRN-P0/+小鼠也显示出对瘙痒病的抵抗力增强。在导入叙利亚仓鼠PrP基因后，PRN-P0/0小鼠对仓鼠高度敏感，但对小鼠蛋白不敏感。这些实验表明，PrP(C)可能接近正常水平，是常见的瘙痒病易感性所必需的，传入的Prion和宿主的PrP基因之间缺乏同源性会延缓疾病。
S. B. Prusiner proposed that the infectious agent of scrapie, the prion, is PrP(Sc), a modified form of the normal host protein PrP(C). Prn-p0/0 mice devoid of PrP(C) showed normal development and behavior. When inoculated with mouse scrapie prions, they remained free of scrapie symptoms for at least 13 months while wild-type controls all died within 6 months. Surprisingly, heterozygous Prn-p0/+ mice also showed enhanced resistance to scrapie. After introduction of Syrian hamster PrP transgenes, Prn-P0/0 mice became highly susceptible to hamster but not to mouse prions. These experiments show that PrP(C), possibly at close to normal levels, is required for the usual susceptibility to scrapie and that lack of homology between incoming prions and the host's PrP genes retards disease.