88220 20210310171107.0 doi 10.1007/s12035-019-1535-0 sideral 111305 ART-2019-111305 eng (orcid)0000-0001-9075-2764 Otero, A. A Single Amino Acid Substitution, Found in Mammals with Low Susceptibility to Prion Diseases, Delays Propagation of Two Prion Strains in Highly Susceptible Transgenic Mouse Models 2019 Access copy available to the general public Unrestricted Specific variations in the amino acid sequence of prion protein (PrP) are key determinants of susceptibility to prion diseases. We previously showed that an amino acid substitution specific to canids confers resistance to prion diseases when expressed in mice and demonstrated its dominant-negative protective effect against a variety of infectious prion strains of different origins and characteristics. Here, we show that expression of this single amino acid change significantly increases survival time in transgenic mice expressing bank vole cellular prion protein (PrP C ), which is inherently prone to misfolding, following inoculation with two distinct prion strains (the CWD-vole strain and an atypical strain of spontaneous origin). This amino acid substitution hinders the propagation of both prion strains, even when expressed in the context of a PrP C uniquely susceptible to a wide range of prion isolates. Non-inoculated mice expressing this substitution experience spontaneous prion formation, but showing an increase in survival time comparable to that observed in mutant mice inoculated with the atypical strain. Our results underscore the importance of this PrP variant in the search for molecules with therapeutic potential against prion diseases. info:eu-repo/grantAgreement/ES/MINECO-FEDER/AGL2015-65560-R info:eu-repo/grantAgreement/ES/MINECO-FEDER/AGL2015-65046-C2-1-R info:eu-repo/grantAgreement/EUR/INTERREG-POCTEFA/EFA-148-16 REDPRION info:eu-repo/grantAgreement/ES/DGA/C020-2014 info:eu-repo/semantics/openAccess All rights reserved http://www.europeana.eu/rights/rr-f/ 4.5 2019 NEUROSCIENCES 65 / 271 = 0.24 2019 Q1 T1 1.482 2019 Neurology 2019 Q1 Neuroscience (miscellaneous) 2019 Q1 Cellular and Molecular Neuroscience 2019 Q2 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion (orcid)0000-0002-0827-110X Hedman, C. Fernández-Borges, N. Eraña, H. (orcid)0000-0002-1590-3347 Marín, B. Universidad de Zaragoza (orcid)0000-0002-2787-9671 Monzón, M. Universidad de Zaragoza Sánchez-Martín, M.A. Nonno, R. (orcid)0000-0002-7173-7216 Badiola, J.J. Universidad de Zaragoza (orcid)0000-0002-2746-3932 Bolea, R. Universidad de Zaragoza Castilla, J. 1009 773 Universidad de Zaragoza Dpto. Patología Animal Área Sanidad Animal 1003 443 Universidad de Zaragoza Dpto. Anatom.Histolog.Humanas Area Histología (2019), 1-11 Mol. neurobiol. MOLECULAR NEUROBIOLOGY 0893-7648 698930 http://zaguan.unizar.es/record/88220/files/texto_completo.pdf Postprint 193460 http://zaguan.unizar.es/record/88220/files/texto_completo.jpg?subformat=icon icon Postprint oai:zaguan.unizar.es:88220 articulos driver 2021-03-10-17:01:20 ARTICLE