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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Ectopic expression of prion protein (PrP) in T lyophocytes or hepatocytes of PrP knockout mice is insufficient to sustain prion replication
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Ectopic expression of prion protein (PrP) in T lyophocytes or hepatocytes of PrP knockout mice is insufficient to sustain prion replication

机译：PrP基因敲除小鼠的T淋巴细胞或肝细胞中ion病毒蛋白（PrP）的异位表达不足以维持病毒复制

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摘要

The cellular form of the Prion protein (Prpo) is necessary for prion replication in mice. To determine whether it is also sufficient, we expressed PrP under the control of various cell- or tissue-specific regulatory elements in PrP knockout mice. The interferon regulatory factor promoter/EP enhancer led to high PrP Ievels in the spleen and low PrP levels in the brain. Following i.p. scrapie inoculation, high prion titers were found in the spleen but not in the brain at 2 weeks and 6 months, showing that the lymphoreticular system by itself is competent to replicate prions. PrP expression directed by the lck promoter resulted in high PrP Ievels on T lymphocytes only but, surprisingly, did not allow prion replication in the thymus, spleen, or brain following i.p. inoculation. A third transgenic line, which expressed PrP in the liver under the control of the albumin promoter/enhancer albeeit at low levels-also failed to replicate prions. These results show that expression of PrP alone is not sufficient to sustain prion replication and suggest that additional components are needed.
机译：Prion蛋白（Prpo）的细胞形式对于小鼠中病毒的复制是必需的。为了确定是否还足够，我们在PrP基因敲除小鼠的各种细胞或组织特异性调节元件的控制下表达了PrP。干扰素调节因子启动子/ EP增强剂导致脾脏中的PrP升高，大脑中的PrP降低。继i.p.接种瘙痒病后，在2周和6个月的脾脏中发现了高病毒滴度，但在大脑中却没有，这表明淋巴网状系统本身能够复制病毒。由lck启动子指导的PrP表达仅在T淋巴细胞上导致高PrP Ievel，但令人惊讶的是，在i.p.之后，不允许ion病毒在胸腺，脾脏或大脑中复制。接种。在低水平的白蛋白启动子/增强子的控制下，在肝脏中表达PrP的第三个转基因品系也未能复制病毒。这些结果表明，仅PrP的表达不足以维持病毒的复制，并表明需要其他组分。

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