Ectopic expression of prion protein (PrP) in T lymphocytes or hepatocytes of PrP knockout mice is insufficient to sustain prion replication

The cellular form of the Prion protein (PrPC) is necessary for prion replic ation 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/E mu enha ncer 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 spl een but not in the brain at 2 weeks and 6 months, showing that the lymphore ticular system by itself is competent to replicate prions, PrP expression d irected by the Lck promoter resulted in high PrP levels on T lymphocytes on ly but, surprisingly, did not allow prion replication in the thymus, spleen , or brain following i.p, inoculation. A third transgenic line, which expre ssed PrP in the liver under the control of the albumin promoter/enhancer-al beit 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.