在表达人类和仿真PrP转基因的小鼠中,子的传播意味着细胞PrP与另一种蛋白质的相互作用
G C Telling1, M Scott, J Mastrianni
1Department of Neurology, University of California, San Francisco 94143, USA.
Cell
|October 6, 1995
概括
表达人类蛋白 (PrP) 的转基因小鼠对人类子有抗性. 一种特定物种的分子,蛋白X,可能在子形成中充当伴侣.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 子疾病涉及子蛋白 (PrP) 的错误折叠.
- 了解细胞PrP (PrPC) 转化为与疾病相关的形式 (PrPSc) 对于开发治疗方法至关重要.
研究的目的:
- 为了研究PrPC转化为PrPSc的机制.
- 为了确定参与子形成和物种障碍的因素.
主要方法:
- 转基因小鼠表达人类 (HuPrP) 和化学蛋白蛋白基因的生成.
- 用人类病脑部提取物注射小鼠.
- 在转基因模型中对小鼠PrP (MoPrP) 的基因切除.
主要成果:
- 转基因 (HuPrP) 的小鼠表达高水平的HuPrPC对人类子具有抗性.
- 在Tg(HuPrP) 小鼠中对人类子的敏感性是通过MoPrP基因的切除而实现的.
- 表达低水平的模拟转基因的小鼠是易感的,在MoPrP基因中断后,化时间略有减少.
- PrPSc 结合 PrPC 在代码子 96-167 之间,而 PrPC 结合 C 末端附近的 X 蛋白.
结论:
- 一种特定于物种的宏分子,称为蛋白X,参与了子的形成.
- 蛋白X可以作为 PrPC 转化为 PrPSc 的分子伴侣.
- 这些发现揭示了子病的机制和物种障碍.
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