NR AXUL
AU Piccardo,P.; Manson,J.C.; King,D.; Ghetti,B.; Barron,R.M.
TI Murine Model of PrP-amyloid Formation without Spongiform Degeneration
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.67
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Background: Prion diseases or transmissible spongiform encephalopathies (TSE) are characterized by the accumulation of PrP-TSE, which serves as a diagnostic marker of disease, and its detection usually indicates the presence of TSE infectivity.
Aim: We studied the relationship between PrP-TSE and infectivity in transgenic (Tg) mice expressing mutant human PrP101L.
Methods: We performed bioassays in Tg 101L mice using brain extracts from 2 cases of GSS P102L having phenotypically different forms of disease.
Results: Brain extracts from a patient with PrP-amyloid plaques and spongiform degeneration transmitted a spongiform encephalopathy to all Tg 101L mice inoculated. Similar results were obtained in mice inoculated with those mouse brains. In contrast, only 1/22 mice developed any disease 622 days after inoculation with brain from a second patient having PrP-amyloid without spongiform degeneration. Surprisingly, many mice without disease nonetheless had PrP-amyloid plaques in their brains, perhaps reflecting subclinical TSE; PrP-TSE was found by immunoblot analysis in one of them. Tg 101L mice inoculated with brain homogenates from an asymptomatic Tg 101L mouse with amyloid plaques did not develop disease. Several of the Tg 101L passage mice also had PrP-amyloid plaques. We did not observe PrP-
TSE in most brains tested, even after precipitation with NaPTA, digestions using less PK, or digestions with PK at 4oC. We also detected no PrP-TSE by DELFIA(R) or antigen capture enzyme immunoassays. Third passaging experiments are underway.
Conclusion: PrP-amyloid accumulated in the brain of Tg mice inoculated with brain homogenate from a human prion disease without causing either clinical illness or spongiform degeneration. Mouse brains containing PrP-amyloid induced appearance of more PrP-amyloid when passaged in mice. These results suggest several possibilities: (i) very low levels of infectivity might be present in Tg mice with PrPamyloid plaques, (ii) under some circumstance, PrP-amyloid might dissociate from infectivity, (iii) PrP-amyloid might sometimes sequester infectious particles into inert aggregates, or (iv) 101L-PrP-amyloid might aggregate and precipitate without acquiring other properties of a self-replicating TSE agent.
AD P. Piccardo, OBRR, CBER, Food and Drug Administration, Lab Bacterial Parasitic Unconventional Agents, USA; J. Manson, D. King, R. Barron, Roslin Institute, Neuropathogenesis Unit, UK; B. Ghetti, Indiana University School of Medicine, Department of Pathology, USA
SP englisch
PO Schottland