NR ASVR
AU Buschmann,A.; Groschup,M.H.
TI Highly bovine spongiform encephalopathy-sensitive transgenic mice confirm the essential restriction of infectivity to the nervous system in clinically diseased cattle
QU Journal of Infectious Diseases 2005 Sep 1; 192(5): 934-42
PT journal article
AB Transgenic mice expressing bovine prion protein (PrP)(C) (Tgbov XV mice) display remarkably shorter incubation times for cattle-derived bovine spongiform encephalopathy (BSE) infectivity than do nontransgenic mice. To verify that this phenomenon reflects increased sensitivity, we challenged Tgbov XV mice and conventional RIII mice with a BSE brain-stem homogenate of known infectivity titer in cattle. An end-point titration experiment in Tgbov XV mice revealed their superior sensitivity, which exceeded that of RIII mice by at least 10,000-fold and even that of cattle by approximately 10-fold. Moreover, Tgbov XV mice were challenged with various tissues from cattle with end-stage clinical BSE, and infectivity was found only in the central and peripheral nervous system and not in lymphatic tissues; the only exception was the Peyer's patches of the distal ileum, which most likely are the site of entry for BSE infectivity. These results provide further indication that the pathogenesis of BSE in cattle is fundamentally different from that in sheep and mice, due to an exclusive intraneuronal spread of infectivity from the gut to the central nervous system.
IN Wertvolle neue Modellsysteme der experimentellen TSE-Forschung sind transgene Mäuse, die Rinderprionprotein exprimieren. Sie sind für BSE-Infektionen mindestens 10.000 empfänglicher als RIII-Mäuse und sogar rund 10-fach emfänglicher als Rinder. Außerdem zeichnen sie sich durch sehr kurze Inkubationszeiten aus. Zur Überprüfung früherer Negativ-Ergebnisse inokulierte man diese Mäuse mit verschiedenen Geweben BSE-kranker Rinder. Dabei fand man BSE-Infekiosität wiederum nur in zentralem und peripherem Nervengewebe sowie in den Peyer-Plaques des distalen Ileums. Die BSE-Infektiosität scheint also tatsächlich in Rindern das lymphatische Gewebe weitestgehend zu meiden und direkt aus dem Darm in periphere Nerven einzudringen.
MH Animals; Brain/immunology/*metabolism; Cattle; Central Nervous System/immunology/*metabolism; Disease Models, Animal; Encephalopathy, Bovine Spongiform/immunology/*metabolism/transmission; Immunohistochemistry/veterinary; Mice; Mice, Transgenic; Prions/*metabolism; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Species Specificity
AD Friedrich-Loeffler-Institut, Institute for Novel and Emerging Infectious Diseases, Greifswald-Insel Riems, Germany.
SP englisch
PO USA