Spontaneous generation of infectious prion disease in transgenic mice

We generated transgenic mice expressing bovine cellular prion protein (PrPC) with a leucine substitution at codon 113 (113L). This protein is homologous to human protein with mutation 102L, and its genetic link with Gerstmann- Sträussler-Scheinker syndrome has been established. This mutation in bovine PrPC causes a fully penetrant, lethal, spongiform encephalopathy. This genetic disease was transmitted by intracerebral inoculation of brain homogenate from ill mice expressing mutant bovine PrP to mice expressing wild-type bovine PrP, which indicated de novo generation of infectious prions. Our findings demonstrate that a single amino acid change in the PrPC sequence can induce spontaneous generation of an infectious prion disease that differs from all others identified in hosts expressing the same PrPC sequence. These observations support the view that a variety of infectious prion strains might spontaneously emerge in hosts displaying random genetic PrPC mutations.

Bibliographic Details

Main Authors:	Torres, J. M., Castilla, J., Pintado, B., Gutiérrez Adán, Alfonso, Andréoletti, O., Aguilar-Calvo, P., Arroba, A. I., Parra-Arrondo, B., Ferrer, I., Manzanares, J., Espinosa Martín, Juan Carlos
Format:	journal article biblioteca
Language:	English
Published:	Centers for Disease Control and Prevention (U.S.) 2013
Online Access:	http://hdl.handle.net/20.500.12792/4536 http://hdl.handle.net/10261/294014
Tags:	Add Tag No Tags, Be the first to tag this record!