Raeber A J, Sailer A, Hegyi I, Klein M A, Rülicke T, Fischer M, Brandner S, Aguzzi A, Weissmann C
Institut für Molekularbiologie, Abteilung I, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3987-92. doi: 10.1073/pnas.96.7.3987.
The cellular form of the Prion protein (PrPC) 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-1 promoter/Emu enhancer led to high PrP levels 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 levels 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-albeit 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.
朊病毒蛋白（PrPC）的细胞形式对于小鼠体内朊病毒的复制是必需的。为了确定其是否也是充分条件，我们在朊病毒蛋白基因敲除小鼠中，在各种细胞或组织特异性调控元件的控制下表达朊病毒蛋白。干扰素调节因子-1启动子/Emu增强子导致脾脏中朊病毒蛋白水平高，而大脑中朊病毒蛋白水平低。腹腔注射羊瘙痒病病原体后，在2周和6个月时，脾脏中发现高朊病毒滴度，而大脑中未发现，这表明淋巴网状系统自身有能力复制朊病毒。由Lck启动子指导的朊病毒蛋白表达仅导致T淋巴细胞上的朊病毒蛋白水平高，但令人惊讶的是，腹腔注射后，胸腺、脾脏或大脑中均未出现朊病毒复制。第三个转基因品系，在白蛋白启动子/增强子的控制下在肝脏中表达朊病毒蛋白——尽管水平较低——也未能复制朊病毒。这些结果表明，仅朊病毒蛋白的表达不足以维持朊病毒的复制，并表明还需要其他成分。
