78258 20200813075838.0 doi 10.1021/acs.analchem.7b03985 sideral 103788 ART-2018-103788 eng Silva, C.J. Determining the Relative Susceptibility of Four Prion Protein Genotypes to Atypical Scrapie 2018 Access copy available to the general public Unrestricted Atypical scrapie is a sheep prion (PrPSc) disease whose epidemiology is consistent with a sporadic origin and is associated with specific polymorphisms of the normal cellular prion protein (PrPC). To determine the relative amounts of PrP polymorphisms present in atypical scrapie, total PrP was digested with chymotrypsin to generate characteristic peptides spanning relevant polymorphisms at positions 136, 141, 154, 171, and 172 of sheep PrPC. A multiple reaction monitoring method (MRM), employing 15N-labeled internal standards, was used to detect and quantify these polymorphisms present in both the PrPSc and PrPC from heterozygous (ALRRY and ALHQY or ALRQD or AFRQY) atypical scrapie-infected or uninfected control sheep. Both polymorphisms of the full length and truncated (C1) natively expressed PrPC are produced in equal amounts. The overall amount of PrPC present in the infected or uninfected animals was similar. PrPSc isolated from heterozygotes was composed of significant amounts of both PrP polymorphisms, including the ALRRY polymorphism which is highly resistant to classical scrapie. Thus, an atypical scrapie infection does not result from an overexpression of sheep PrPC. The replication of all atypical scrapie prions occurs at comparable rates, despite polymorphisms at positions 141, 154, 171, or 172. info:eu-repo/grantAgreement/ES/DGA/A17 info:eu-repo/grantAgreement/ES/MINECO/AGL2015-65560-R info:eu-repo/semantics/openAccess All rights reserved http://www.europeana.eu/rights/rr-f/ 6.35 2018 CHEMISTRY, ANALYTICAL 7 / 84 = 0.083 2018 Q1 T1 2.113 2018 Analytical Chemistry 2018 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Erickson-Beltran, M.L. (orcid)0000-0001-6016-4726 Martín-Burriel, I. Universidad de Zaragoza (orcid)0000-0002-7173-7216 Badiola, J.J. Universidad de Zaragoza Requena, J.R. (orcid)0000-0002-2746-3932 Bolea, R. Universidad de Zaragoza 1001 420 Universidad de Zaragoza Dpto. Anatom.,Embri.Genét.Ani. Área Genética 1009 773 Universidad de Zaragoza Dpto. Patología Animal Área Sanidad Animal 90, 2 (2018), 1255-1262 Anal. chem. ANALYTICAL CHEMISTRY 0003-2700 260989 http://zaguan.unizar.es/record/78258/files/texto_completo.pdf Postprint 73712 http://zaguan.unizar.es/record/78258/files/texto_completo.jpg?subformat=icon icon Postprint oai:zaguan.unizar.es:78258 articulos driver 2020-08-13-07:57:56 ARTICLE