000076051 001__ 76051 000076051 005__ 20220208112845.0 000076051 0247_ $$2doi$$a10.1007/s12035-017-0832-8 000076051 0248_ $$2sideral$$a103787 000076051 037__ $$aART-2017-103787 000076051 041__ $$aeng 000076051 100__ $$0(orcid)0000-0001-9075-2764$$aOtero García, Alicia$$uUniversidad de Zaragoza 000076051 245__ $$aAn amino acid substitution found in animals with low susceptibility to prion diseases confers a protective dominant-negative effect in prion-infected transgenic mice 000076051 260__ $$c2017 000076051 5060_ $$aAccess copy available to the general public$$fUnrestricted 000076051 5203_ $$aWhile prion diseases have been described in numerous species, some, including those of the Canidae family, appear to show resistance or reduced susceptibility. A better understanding of the factors underlying prion susceptibility is crucial for the development of effective treatment and control measures. We recently demonstrated resistance to prion infection in mice overexpressing a mutated prion protein (PrP) carrying a specific amino acid substitution characteristic of canids. Here, we show that coexpression of this mutated PrP and wild-type mouse PrP in transgenic mice inoculated with different mouse-adapted prion strains (22 L, ME7, RML, and 301C) significantly increases survival times (by 45 to 113%). These data indicate that this amino acid substitution confers a dominant-negative effect on PrP, attenuating the conversion of PrPC to PrPSc and delaying disease onset without altering the neuropathological properties of the prion strains. Taken together, these findings have important implications for the development of new treatment approaches for prion diseases based on dominant-negative proteins. 000076051 536__ $$9info:eu-repo/grantAgreement/ES/DGA/C020-2014$$9info:eu-repo/grantAgreement/ES/MINECO/AGL2015-65046-C2-1-R$$9info:eu-repo/grantAgreement/ES/MINECO/AGL2015-65560-R$$9info:eu-repo/grantAgreement/ES/MINECO/PCIN-2013-065$$9info:eu-repo/grantAgreement/ES/MINECO/SEV-2016-0644 000076051 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/ 000076051 590__ $$a5.076$$b2017 000076051 591__ $$aNEUROSCIENCES$$b44 / 261 = 0.169$$c2017$$dQ1$$eT1 000076051 592__ $$a1.614$$b2017 000076051 593__ $$aNeurology$$c2017$$dQ1 000076051 593__ $$aNeuroscience (miscellaneous)$$c2017$$dQ1 000076051 593__ $$aCellular and Molecular Neuroscience$$c2017$$dQ2 000076051 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion 000076051 700__ $$0(orcid)0000-0002-2746-3932$$aBolea Bailo, Rosa$$uUniversidad de Zaragoza 000076051 700__ $$0(orcid)0000-0002-0827-110X$$aHedman Altamirano, Carlos 000076051 700__ $$aFernández-Borges, Natalia 000076051 700__ $$0(orcid)0000-0002-1590-3347$$aMarín González, María Belén$$uUniversidad de Zaragoza 000076051 700__ $$0(orcid)0000-0003-2454-2114$$aLópez Pérez, Óscar$$uUniversidad de Zaragoza 000076051 700__ $$0(orcid)0000-0002-7037-6316$$aBarrio Alegre, Tomás$$uUniversidad de Zaragoza 000076051 700__ $$aEraña, Hasier 000076051 700__ $$aSánchez-Martín, Manuel A. 000076051 700__ $$0(orcid)0000-0002-2787-9671$$aMonzón Garcés, Marta$$uUniversidad de Zaragoza 000076051 700__ $$0(orcid)0000-0002-7173-7216$$aBadiola Díez, Juan José$$uUniversidad de Zaragoza 000076051 700__ $$aCastilla, Joaquín 000076051 7102_ $$11001$$2420$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Genética 000076051 7102_ $$11009$$2773$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Sanidad Animal 000076051 7102_ $$11003$$2443$$aUniversidad de Zaragoza$$bDpto. Anatom.Histolog.Humanas$$cArea Histología 000076051 773__ $$g55, 7 (2017), 6182-6192$$pMol. neurobiol.$$tMOLECULAR NEUROBIOLOGY$$x0893-7648 000076051 8564_ $$s1966143$$uhttps://zaguan.unizar.es/record/76051/files/texto_completo.pdf$$yPostprint 000076051 8564_ $$s63878$$uhttps://zaguan.unizar.es/record/76051/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint 000076051 909CO $$ooai:zaguan.unizar.es:76051$$particulos$$pdriver 000076051 951__ $$a2022-02-08-11:23:42 000076051 980__ $$aARTICLE