Prion protein of 106 residues creates an artificial transmission barrier for prion replication in transgenic mice
Prion protein of 106 residues creates an artificial transmission barrier for prion replication in transgenic mice
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DOI：
10.1016/s0092-8674(00)80596-6
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发表时间：
1999-03-19
期刊：
影响因子：
64.5
通讯作者：
Scott, M
中科院分区：
文献类型：
--
作者：
Supattapone, S;Bosque, P;Scott, M
在缺乏野生型(Wt)PrP(PRNP(0/0))的转基因(TG)小鼠中表达了一个含有106个氨基酸的编辑后的PrP蛋白(PrP)，并支持了PrP的繁殖。含有全长PrPSc的RML Prion在类似的300天后在TG(PrP106)PRNP(0/0)小鼠中产生疾病，而含有PrP(SC)106的RML106 Prion在重复传代仅类似于65天后在TG(PrP106)PRNP(0/0)小鼠中产生疾病。在发生瘙痒病的TG(PrP106)PRNP(+/0)小鼠中，wt MoPrPC的共表达降低了RML Prion通过的这种人工传递障碍，这表明wt MoPrP通过反式作用加速RML106 Prion的复制。纯化的PrP(SC)106不溶于非变性洗涤剂，具有抗蛋白酶活性，可形成丝状结构。RML106 Prion的独特特征提供了对Prion复制机制的洞察，而PrP(SC)106的小尺寸应该有助于结构分析。
A redacted prion protein (PrP) of 106 amino acids with two large deletions was expressed in transgenic (Tg) mice deficient for wild-type (wt) PrP (Prnp(0/0)) and supported prion propagation. RML prions containing full-length PrPSc produced disease in Tg(PrP106)Prnp(0/0) mice after similar to 300 days, while transmission of RML106 prions containing PrP(Sc)106 created disease in Tg(PrP106) Prnp(0/0) mice after only similar to 65 days on repeated passage. This artificial transmission barrier for the passage of RML prions was diminished by the coexpression of wt MoPrPC in Tg(PrP106)Prnp(+/0) mice that developed scrapie in similar to 165 days, suggesting that wt MoPrP acts in trans to accelerate replication of RML106 prions. Purified PrP(Sc)106 was protease resistant, formed filaments, and was insoluble in nondenaturing detergents. The unique features of RML106 prions offer insights into the mechanism of prion replication, and the small size of PrP(Sc)106 should facilitate structural analysis.