title: Gerstmann-Sträussler-Scheinker disease subtypes efficiently transmit in bank voles as genuine prion diseases.
abstract: Gerstmann-Sträussler-Scheinker disease (GSS) is an inherited neurodegenerative disorder associated with mutations in the prion protein gene and accumulation of misfolded PrP with protease-resistant fragments (PrP(res)) of 6-8 kDa. With the exception of a few GSS cases characterized by co-accumulation of PrP(res) of 21 kDa, efforts to transmit GSS to rodents have been unsuccessful. As a result, GSS subtypes exclusively associated with 6-8 kDa PrP(res) have often been considered as non-transmissible proteinopathies rather than true prion diseases. We show that GSS with P102L, A117V and F198S mutations transmit efficiently and produce distinct pathological phenotypes in bank voles (M. glareolus), irrespective of the presence of 21 kDa PrP(res) in the inoculum, demonstrating that GSS is a genuine prion disease characterized by both transmissibility and strain variation.
authors: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
authors: Laura
authors: L
authors: Pirisinu
authors: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
authors: Michele A
authors: MA
authors: Di Bari
authors: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
authors: Claudia
authors: C
authors: D'Agostino
authors: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
authors: Stefano
authors: S
authors: Marcon
authors: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
authors: Geraldina
authors: G
authors: Riccardi
authors: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
authors: Anna
authors: A
authors: Poleggi
authors: Department of Pathology, National Prion Disease Pathology Surveillance Center, Case Western Reserve University, School of Medicine, 2085 Adelbert Road Cleveland, Ohio, OH 44106, USA.
authors: Mark L
authors: ML
authors: Cohen
authors: Department of Pathology, National Prion Disease Pathology Surveillance Center, Case Western Reserve University, School of Medicine, 2085 Adelbert Road Cleveland, Ohio, OH 44106, USA.
authors: Brian S
authors: BS
authors: Appleby
authors: Department of Pathology, National Prion Disease Pathology Surveillance Center, Case Western Reserve University, School of Medicine, 2085 Adelbert Road Cleveland, Ohio, OH 44106, USA.
authors: Pierluigi
authors: P
authors: Gambetti
authors: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors: Bernardino
authors: B
authors: Ghetti
authors: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
authors: Umberto
authors: U
authors: Agrimi
authors: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
authors: Romolo
authors: R
authors: Nonno
mesh_terms: D000818:Animals; D003411:Arvicolinae; D004195:Disease Models, Animal; D016098:Gerstmann-Straussler-Scheinker Disease / Q000235:genetics / Q000473:pathology*; D006801:Humans; D009154:Mutation; D000072002:Prion Proteins / Q000235:genetics*
chemical_list: D000072002:Prion Proteins