title: Variably protease-sensitive prionopathy, a unique prion variant with inefficient transmission properties.
abstract: Variably protease-sensitive prionopathy (VPSPr) can occur in persons of all codon 129 genotypes in the human prion protein gene (PRNP) and is characterized by a unique biochemical profile when compared with other human prion diseases. We investigated transmission properties of VPSPr by inoculating transgenic mice expressing human PRNP with brain tissue from 2 persons with the valine-homozygous (VV) and 1 with the heterozygous methionine/valine codon 129 genotype. No clinical signs or vacuolar pathology were observed in any inoculated mice. Small deposits of prion protein accumulated in the brains of inoculated mice after challenge with brain material from VV VPSPr patients. Some of these deposits resembled microplaques that occur in the brains of VPSPr patients. Comparison of these transmission properties with those of sporadic Creutzfeldt-Jakob disease in the same lines of mice indicated that VPSPr has distinct biological properties. Moreover, we established that VPSPr has limited potential for human-to-human transmission.
authors.forename: Abigail B
authors.initials: AB
authors.lastname: Diack
authors.forename: Diane L
authors.initials: DL
authors.lastname: Ritchie
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Peden
authors.forename: Deborah
authors.initials: D
authors.lastname: Brown
authors.forename: Aileen
authors.initials: A
authors.lastname: Boyle
authors.forename: Laura
authors.initials: L
authors.lastname: Morabito
authors.forename: David
authors.initials: D
authors.lastname: Maclennan
authors.forename: Paul
authors.initials: P
authors.lastname: Burgoyne
authors.forename: Casper
authors.initials: C
authors.lastname: Jansen
authors.forename: Richard S
authors.initials: RS
authors.lastname: Knight
authors.forename: Pedro
authors.initials: P
authors.lastname: Piccardo
authors.forename: James W
authors.initials: JW
authors.lastname: Ironside
authors.forename: Jean C
authors.initials: JC
authors.lastname: Manson
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D014644:Genetic Variation; D005838:Genotype; D005911:Gliosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D017096:Prion Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000635:transmission*; D011328:Prions / Q000235:genetics* / Q000378:metabolism
chemical_list: D011328:Prions