title: Spontaneous generation of infectious prion disease in transgenic mice.
abstract: We generated transgenic mice expressing bovine cellular prion protein (PrP(C)) 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 PrP(C) 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 PrP(C) sequence can induce spontaneous generation of an infectious prion disease that differs from all others identified in hosts expressing the same PrP(C) sequence. These observations support the view that a variety of infectious prion strains might spontaneously emerge in hosts displaying random genetic PrP(C) mutations.
authors.forename: Juan-María
authors.initials: JM
authors.lastname: Torres
authors.forename: Joaquín
authors.initials: J
authors.lastname: Castilla
authors.forename: Belén
authors.initials: B
authors.lastname: Pintado
authors.forename: Alfonso
authors.initials: A
authors.lastname: Gutiérrez-Adan
authors.forename: Olivier
authors.initials: O
authors.lastname: Andréoletti
authors.forename: Patricia
authors.initials: P
authors.lastname: Aguilar-Calvo
authors.forename: Ana-Isabel
authors.initials: AI
authors.lastname: Arroba
authors.forename: Beatriz
authors.initials: B
authors.lastname: Parra-Arrondo
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
authors.forename: Jorge
authors.initials: J
authors.lastname: Manzanares
authors.forename: Juan-Carlos
authors.initials: JC
authors.lastname: Espinosa
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D016643:Encephalopathy, Bovine Spongiform / Q000235:genetics / Q000473:pathology / Q000635:transmission; D015870:Gene Expression; D005838:Genotype; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D016366:Open Reading Frames; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism; D017096:Prion Diseases / Q000235:genetics* / Q000473:pathology / Q000635:transmission
chemical_list: D018620:PrPSc Proteins
keywords: BSE; Gerstmann–Sträussler–Scheinker syndrome; TSE; bovine PrP; bovine prion protein; bovine spongiform encephalopathy; prions and related diseases; spontaneous generation; transgenic mice; transmissible spongiform encephalopathy