NR AJRT
AU Prusiner,S.B.; Scott,M.R.D.; Foster,D.B.; Pan,K.M.; Groth,D.; Mirenda,C.; Torchia,M.; Yang,S.L.; Serban,D.; Carlson,G.A.; Hoppe,P.C.; Westaway,D.; DeArmond,S.J.
TI Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication
QU Cell 1990 Nov 16; 63(4): 673-86
PT journal article
AB Transgenic (Tg) mice expressing both Syrian hamster (Ha) and mouse (Mo) prion protein (PrP) genes were used to probe the mechanism of scrapie prion replication. Four Tg lines expressing HaPrP exhibited distinct incubation times ranging from 48 to 277 days, which correlated inversely with HaPrP mRNA and HaPrPc. Bioassays of Tg brain extracts showed that the prion inoculum dictates which prions are synthesized de novo. Tg mice inoculated with Ha prions had approximately 10(9) ID50 units of Ha prions per gram of brain and less than 10 units of Mo prions. Conversely, Tg mice inoculated with Mo prions synthesized Mo prions but not Ha prions. Similarly, Tg mice inoculated with Ha prions exhibited neuropathologic changes characteristic of hamsters with scrapie, while Mo prions produced changes similar to those in non-Tg mice. Our results argue that species specificity of scrapie prions resides in the PrP sequence and prion synthesis is initiated by a species-specific interaction between PrPsc in the inoculum and homologous PrPc.
IN Transgene Mäuse mit einem zusätzlichen Gen für das Hamsterprionprotein werden nach Prioninfektionen umso schneller krank, je stärker ihre Prionproteine exprimiert werden. Dabei bestimmt der Typ der infizierenden Prione, welcher Typ von Prionen neu synthetisiert wird. Inokulierte Hamsterprione induzieren die Neusynthese von fast ausschließlich Hamsterprionen. Es werden aber auch in geringem Ausmaß Mausprione gebildet, die dann wahrscheinlich ihrerseits die Neubildung weiterer Mausprione induzieren. Die Inokulation mit Mausprionen bewirkt umgekehrt fast ausschließlich die Neusynthese von Mausprionen. Die Speziesspezifität der Krankheitsübertragung hängt demnach von der Homologie der zelleigenen und der übertragenen Prionproteine ab und ist offenbar nicht absolut unüberwindbar.
MH Animal; Blotting, Northern; Blotting, Western; Brain/metabolism/microbiology/pathology; Enzyme-Linked Immunosorbent Assay; Hamsters; Mesocricetus; Mice; Mice, Transgenic; Nerve Degeneration; PrPsc Proteins; Prions/*genetics/physiology; RNA, Messenger/genetics; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Transcription, Genetic; Viral Proteins/*genetics; *Virus Replication
AD Dallas Foster, Darlene Groth, Carol Mirenda, Keh-Ming Pan, Stanley B. Prusiner, Michael Scott, Dan Serban, Marilyn Torchia, David Westaway, Shu-Lian Yang, Department of Neurology University of California, San Francisco, California 94143, USA; Stanley B. Prusiner, Department of Biochemistry and Biophysics University of California, San Francisco, California 94143, USA; Shu-Lian Yang, Stephen J. DeArmond, Department of Pathology University of California, San Francisco, California 94143, USA; George A. Carlson, McLaughlin Research Institute, Great Falls, Montana 59401, USA; Peter C. Hoppe, Jackson Laboratory, Bar Harbor, Maine 04609, USA
SP englisch
PO USA