NR AKIL
AU Sakaguchi,S.; Katamine,S.; Shigematsu,K.; Nakatani,A.; Moriuchi,R.; Nishida,N.; Kurokawa,K.; Nakaoke,R.; Sato,H.; Jishage,K.; Kuno,J.; Noda,T.; Miyamoto,T.
TI Accumulation of proteinase K-resistant prion protein (PrP) is restricted by the expression level of normal PrP in mice inoculated with a mouse-adapted strain of the Creutzfeldt-Jakob disease agent
QU Journal of Virology 1995 Dec; 69(12): 7586-92
PT journal article
AB Creutzfeldt-Jakob disease (CJD) is a transmissible neurodegenerative disease of humans caused by an unidentified infectious agent, the prion. To determine whether there was an involvement of the host-encoded prion protein (PrPc) in CJD development and prion propagation, mice heterozygous (PrP+/-) or homozygous (PrP-/-) for a disrupted PrP gene were established and inoculated with the mouse-adapted CJD agent. In keeping with findings of previous studies using other lines of PrP-less mice inoculated with scrapie agents, no PrP-/- mice showed any sign of the disease for 460 days after inoculation, while all of the PrP+/- and control PrP+/+ mice developed CJD-like symptoms and died. The incubation period for PrP+/- mice, 259 +/- 27 days, was much longer than that for PrP+/+ mice, 138 +/- 12 days. Propagation of the prion was barely detectable in the brains of PrP-/- mice and was estimated to be at a level at least 4 orders of magnitude lower than that in PrP+/+ mice. These findings indicate that PrPc is necessary for both the development of the disease and propagation of the prion in the inoculated mice. The proteinase-resistant PrP (PrPres) was undetectable in the brain tissues of the inoculated PrP-/- mice, while it accumulated in the affected brains of PrP+/+ and PrP+/- mice. Interestingly, the maximum level of PrPres in the brains of PrP+/- mice was about half of the level in the similarly affected brains of PrP+/+ mice, indicating that PrPres accumulation is restricted by the level of PrPc.
IN Infektiöses Material (Gehirn) von Mäusen mit einer ursprünglich durch CJD-Gewebe verursachten scrapieartigen Krankheit ließ Mäuse ohne Prionproteine selbst nach 460 Tagen nicht an Scrapie, Mäuse mit nur einem funktionierenden Prionproteingen nach durchschnittlich 259+/-27 Tagen und normale Mäuse bereits nach 138+/-12 Tagen an Scrapie sterben. Die Akkumulation des Erregers konnte in Mäusen ohne Prionproteine garnicht beobachtet werden und erreichte in Mäusen mit nur einem funktionierenden Prionproteingen nur die Hälfte des normalen Ausmaßes.
ZR 37
MH Animal; Brain/pathology/virology; Cloning, Molecular; Creutzfeldt-Jakob Syndrome/pathology/*virology; DNA Probes; DNA, Viral/analysis/biosynthesis; Endopeptidase K; *Gene Expression; Hamsters; Human; In Situ Hybridization; Mice; Mice, Mutant Strains; Prions/biosynthesis/genetics/*metabolism; Restriction Mapping; Serine Endopeptidases/*metabolism; Stem Cells/physiology; Support, Non-U.S. Gov't; Time Factors
AD Department of Bacteriology, Nagasaki University School of Medicine, Japan.
SP englisch
PO USA
OR Prion-Krankheiten 7