NR AMIM
AU Weissmann,C.; Büeler,H.; Fischer,M.; Sailer,A.; Aguzzi,A.; Aguet,M.
TI PrP-deficient mice are resistant to scrapie
QU Slow Infections of the Central Nervous System (Ed. Bjornsson, J.; Carp, R.I.; Love, A.; Wisniewski, H.M.) 1994 Jun 6; 724: 235-40
PT journal article
AB Prusiner proposed that the infectious agent of scrapie, the prion, is PrPsc, a modified form of the normal host protein PrPc. Prn-p0/0 mice devoid of PrPc showed normal development and behavior. When inoculated with mouse scrapie prions they remained free of scrapie symptoms for at least 16 months while wild type controls all died within 6 months. Propagation of infectivity in the PrP null mice, if any, was less than 10(-5) that in wild type animals. Surprisingly, heterozygous Prn-p0/+ mice also showed enhanced resistance to scrapie. After introduction of Syrian hamster PrP transgenes, Prn-p0/0 mice became highly susceptible to hamster but not to mouse prions. These experiments show that PrPc, possibly at close to normal levels, is required for the usual susceptibility to scrapie and that lack of homology between incoming prions and the host's PrP genes retards disease.
IN Mit Maus-Scrapie infizierte Mäuse ohne eigene Prionproteine blieben inzwischen 16 Monate ohne Symptome, während alle normalen Kontroll-Mäuse binnen 6 Monaten starben. Es konnte keine Vermehrung der Infektiosität in den Prn-p0/0-Mäusen festgestellt werden. Auch Mäuse mit nur einem intakten Prionproteingen waren resistenter gegenüber Prion-Infektionen. Transgene Prn-p0/0-Mäuse mit einem Hamster-Prionproteingen konnten durch Hamster, jedoch nicht durch Mausprione infiziert werden.
MH Animal; Brain/metabolism/microbiology/pathology; Genetic Complementation Test; Hamsters; Immunity, Natural; Mesocricetus; Mice; Mice, Mutant Strains; *Prions/genetics; Scrapie/genetics/*immunology; Spleen/metabolism/microbiology; Support, Non-U.S. Gov't
AD Prof. Charles Weissmann, Universität Zürich, Institut für Molekularbiologie, Abteilung I, Hönggerberg, 8093 Zürich, Schweiz, Postfach, Tel. 633 24 91, Fax 371 72 05
SP englisch
PO USA