Infection by ME7 prion is not modified in transgenic mice expressing the yeast chaperone Hsp104 in neurons
Infection by ME7 prion is not modified in transgenic mice expressing the yeast chaperone Hsp104 in neurons
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DOI：
10.1016/j.neulet.2006.05.066
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发表时间：
2006-09-25
影响因子：
2.5
通讯作者：
Dron, Michel
中科院分区：
文献类型：
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作者：
Dandoy-Dron, Francoise;Bogdanova, Anna;Dron, Michel
Hsp 104分子伴侣诱导酵母耐热性并拯救聚集体中的蛋白质。在这项研究中，我们表明，异种表达的热休克蛋白104显着增加的神经元小鼠CAD细胞系暴露于热休克后的生存能力。这些结果表明，热休克蛋白104蛋白赋予哺乳动物神经元细胞的耐热性，热休克蛋白104在酵母中的典型属性。Hsp 104还决定了朊病毒样蛋白在酵母中的状态，并研究Hsp 104的表达是否可以在体内改变哺乳动物朊病毒感染，产生了神经元中特异性表达Hsp 104的转基因小鼠。小鼠发育和繁殖正常，它们没有表现出可检测到的身体缺陷，并可能构成有价值的模型，用于研究聚集倾向的神经病理学疾病。Hsp 104转基因和对照同窝仔脑内感染羊瘙痒症的ME 7株。在转基因小鼠和对照小鼠之间没有观察到疾病的孵育时间或PrPSc积累的差异。这些结果表明，热休克蛋白Hsp 104是没有效率的调节哺乳动物朊病毒的增殖和/或抵消神经退行性病变的羊瘙痒病感染的小鼠的大脑。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
The Hsp104 chaperone induces thermo-tolerance in yeast and rescues proteins trapped in aggregates. In this study, we showed that xenogenic expression of Hsp104 dramatically increased the viability of the neuronal mouse CAD cell line after exposure to heat shock. These results indicate that the Hsp104 protein confers thermo-resistance to mammalian neuronal cells, the canonical property of Hsp104 in yeast. Hsp104 also determines the prion state of prion-like proteins in yeast and to investigate whether Hsp104 expression may modify mammalian prion infection in vivo, transgenic mice with specific expression of Hsp104 in neurons were generated. Mice develop and reproduce normally, they show no detectable physical defect and may constitute valuable model for the study of aggregation-prone neuropathological disorders. Hsp104 transgenic and control littermates were infected intracerebrally with the ME7 strain of scrapie. No differences in the incubation time of the disease or in PrPSc accumulation were observed between transgenic and control mice. These results suggest that the heat-shock protein Hsp104 is not efficient to modulate the multiplication of mammalian prions and/or to counteract neurodegeneration in the brain of scrapie-infected mice. (c) 2006 Elsevier Ireland Ltd. All rights reserved.