Gerstmann-Sträussler-Scheinker disease subtypes efficiently transmit in bank voles as genuine prion diseases

• Published in: Scientific reports 2016-02, Vol.6 (1), p.20443-20443, Article 20443
• Main Authors: Pirisinu, Laura, Di Bari, Michele A., D’Agostino, Claudia, Marcon, Stefano, Riccardi, Geraldina, Poleggi, Anna, Cohen, Mark L., Appleby, Brian S., Gambetti, Pierluigi, Ghetti, Bernardino, Agrimi, Umberto, Nonno, Romolo
• Format: Article
• Language: English
• Subjects: 631/378/1689/2609; 64; 692/617/375/1937; 82; 82/29; 82/51; Animals; Arvicolinae; Disease; Disease Models, Animal; Gerstmann-Straussler-Scheinker Disease - genetics; Gerstmann-Straussler-Scheinker Disease - pathology; Humanities and Social Sciences; Humans; Inoculum; multidisciplinary; Mutation; Neurodegenerative diseases; Prion protein; Prion Proteins - genetics; Protein folding; Science
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep20443

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.