NR ALPM
AU Telling,G.C.; Scott,M.R.D.; Hsiao,K.K.; Foster,D.B.; Yang,S.L.; Torchia,M.; Sidle,K.C.L.; Collinge,J.; DeArmond,S.J.; Prusiner,S.B.
TI Transmission of Creutzfeldt-Jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein
QU Proceedings of the National Academy of Sciences of the United States of America 1994 Oct 11; 91(21): 9936-40
PT journal article
AB Transgenic (Tg) mice were constructed that express a chimeric prion protein (PrP) in which a segment of mouse (Mo) PrP was replaced with the corresponding human (Hu) PrP sequence. The chimeric PrP, designated MHu2MPrP, differs from MoPrP by 9 amino acids between residues 96 and 167. All of the Tg(MHu2M) mice developed neurologic disease approximately 200 days after inoculation with brain homogenates from three patients dying of Creutzfeldt-Jakob disease (CJD). Inoculation of Tg(MHu2M) mice with CJD prions produced MHu2MPrPsc (where PrPsc is the scrapie isoform of PrP); inoculation with Mo prions produced Mo-PrPsc. The patterns of MHu2MPrPsc and MoPrPsc accumulation in the brains of Tg(MHu2M) mice were different. About 10% of Tg(HuPrP) mice expressing HuPrP and non-Tg mice developed neurologic disease > 500 days after inoculation with CJD prions. The different susceptibilities of Tg(HuPrP) and Tg(MHu2M) mice to Hu prions indicate that additional species-specific factors are involved in prion replication. Diagnosis, prevention, and treatment of Hu prion diseases should be facilitated by Tg(MHu2M) mice.
IN Es wurden transgene Mäuse erzeugt, bei denen ein Prionproteingen zwischen den Aminosäuren 96 und 167 an 9 Positionen verändert ist, weil es in diesem Bereich dem menschlichen Gen entspricht. Werden diese Mäuse mit menschlichen Prionen infiziert, dann entstehen menschliche Prionen. Infektionen mit Mausprionen führen zur Bildung von Mausprionen. Dabei unterscheiden sich außerdem die Muster der Prionanreicherung.
ZR 58
MH Animal; Astrocytes/metabolism/pathology; Brain/metabolism/*pathology; Chimeric Proteins/analysis/*biosynthesis; Creutzfeldt-Jakob Syndrome/*genetics/pathology/*physiopathology; Human; Mice; Mice, Transgenic; Open Reading Frames; Polymerase Chain Reaction/methods; Prions/analysis/*biosynthesis/genetics; Restriction Mapping; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Time Factors
AD Department of Neurology, University of California, San Francisco 94143.
SP englisch
PO USA
OR Prion-Krankheiten 8