000088220 001__ 88220 000088220 005__ 20210310171107.0 000088220 0247_ $$2doi$$a10.1007/s12035-019-1535-0 000088220 0248_ $$2sideral$$a111305 000088220 037__ $$aART-2019-111305 000088220 041__ $$aeng 000088220 100__ $$0(orcid)0000-0001-9075-2764$$aOtero, A. 000088220 245__ $$aA Single Amino Acid Substitution, Found in Mammals with Low Susceptibility to Prion Diseases, Delays Propagation of Two Prion Strains in Highly Susceptible Transgenic Mouse Models 000088220 260__ $$c2019 000088220 5060_ $$aAccess copy available to the general public$$fUnrestricted 000088220 5203_ $$aSpecific variations in the amino acid sequence of prion protein (PrP) are key determinants of susceptibility to prion diseases. We previously showed that an amino acid substitution specific to canids confers resistance to prion diseases when expressed in mice and demonstrated its dominant-negative protective effect against a variety of infectious prion strains of different origins and characteristics. Here, we show that expression of this single amino acid change significantly increases survival time in transgenic mice expressing bank vole cellular prion protein (PrP C ), which is inherently prone to misfolding, following inoculation with two distinct prion strains (the CWD-vole strain and an atypical strain of spontaneous origin). This amino acid substitution hinders the propagation of both prion strains, even when expressed in the context of a PrP C uniquely susceptible to a wide range of prion isolates. Non-inoculated mice expressing this substitution experience spontaneous prion formation, but showing an increase in survival time comparable to that observed in mutant mice inoculated with the atypical strain. Our results underscore the importance of this PrP variant in the search for molecules with therapeutic potential against prion diseases. 000088220 536__ $$9info:eu-repo/grantAgreement/ES/MINECO-FEDER/AGL2015-65560-R$$9info:eu-repo/grantAgreement/ES/MINECO-FEDER/AGL2015-65046-C2-1-R$$9info:eu-repo/grantAgreement/EUR/INTERREG-POCTEFA/EFA-148-16 REDPRION$$9info:eu-repo/grantAgreement/ES/DGA/C020-2014 000088220 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/ 000088220 590__ $$a4.5$$b2019 000088220 591__ $$aNEUROSCIENCES$$b65 / 271 = 0.24$$c2019$$dQ1$$eT1 000088220 592__ $$a1.482$$b2019 000088220 593__ $$aNeurology$$c2019$$dQ1 000088220 593__ $$aNeuroscience (miscellaneous)$$c2019$$dQ1 000088220 593__ $$aCellular and Molecular Neuroscience$$c2019$$dQ2 000088220 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion 000088220 700__ $$0(orcid)0000-0002-0827-110X$$aHedman, C. 000088220 700__ $$aFernández-Borges, N. 000088220 700__ $$aEraña, H. 000088220 700__ $$0(orcid)0000-0002-1590-3347$$aMarín, B.$$uUniversidad de Zaragoza 000088220 700__ $$0(orcid)0000-0002-2787-9671$$aMonzón, M.$$uUniversidad de Zaragoza 000088220 700__ $$aSánchez-Martín, M.A. 000088220 700__ $$aNonno, R. 000088220 700__ $$0(orcid)0000-0002-7173-7216$$aBadiola, J.J.$$uUniversidad de Zaragoza 000088220 700__ $$0(orcid)0000-0002-2746-3932$$aBolea, R.$$uUniversidad de Zaragoza 000088220 700__ $$aCastilla, J. 000088220 7102_ $$11009$$2773$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Sanidad Animal 000088220 7102_ $$11003$$2443$$aUniversidad de Zaragoza$$bDpto. Anatom.Histolog.Humanas$$cArea Histología 000088220 773__ $$g(2019), 1-11$$pMol. neurobiol.$$tMOLECULAR NEUROBIOLOGY$$x0893-7648 000088220 8564_ $$s698930$$uhttps://zaguan.unizar.es/record/88220/files/texto_completo.pdf$$yPostprint 000088220 8564_ $$s193460$$uhttps://zaguan.unizar.es/record/88220/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint 000088220 909CO $$ooai:zaguan.unizar.es:88220$$particulos$$pdriver 000088220 951__ $$a2021-03-10-17:01:20 000088220 980__ $$aARTICLE