145575 20240423115941.0 DZNE-2020-00908 English 570 Kaczmarczyk, Lech P:(DE-2719)2810486 0 dzne PRION 2019 Edmonton 2019-05-21 - 2019-05-24 Canada Caribou Prnp polymorphism distribution in Canada and its impact on CWD pathogenesis 2019 Abstract abstract abstract PUB:(DE-HGF)1 1713784899_6653 PUB:(DE-HGF) Conference Paper 33 EndNote INPROCEEDINGS BibTeX conferenceObject DRIVER Journal Article PUB:(DE-HGF)16 PUB:(DE-HGF) journal Output Types/Conference Abstract DataCite OTHER ORCID Wild reindeer in Norway were recently diagnosed withchronic wasting disease (CWD) [1]. Prions from CWD-infected deer were also transmissible to other reindeer inexperimental settings [2,3]. Although CWD has not yetbeen reported in wild reindeer (caribou) in Canada, thesestudies show that they are at risk of infection. The wild-typereindeer, homozygous for serine at prion protein (PrP)residue 138 (138SS), developed clinical disease upon oralinoculation. Animals carrying at least one asparagine allele(138SN, 138NN) accumulated prions only in the periphery.However, both genotypes were susceptible to intracerebralprion inoculation [2,3]. Fallow deer are wild-type 138NNand are resistant to peripheral but not intracerebral prioninfection [4]. Thus, we hypothesize that the138N allele,present in caribou herds in Alberta [5], alters CWD patho-genesis by limiting prion transport from the periphery tothe CNS. Our aim is to elucidate the mechanisms involvedin this process.We extracted DNA from ±800 caribou, sequenced thePrnpopen reading frame and determined the 138N alleleprevalence in Canadian caribou populations. Resultsshow that the 138N allele was highly prevalent in theChinchaga woodland caribou population in BC (64%). Itwas also higher in barren-ground (37%) than in otherwoodland caribou populations (26%). To analyse howthe 138N allele affects CWD pathogenesis, we generatedknock-in (KI) mice where the mouse PrP is replaced bywild-type 138SS or 138NN cervid PrP. The KIs wereobtained by injecting CRISPR/Cas9-edited C57BL6embryonic stem cells (Bruce4) into wild-type blastocysts,generating chimeras, and breeding progeny to homozyg-osity in a C57BL6 background. PrP expression was deter-mined using western blotting and qPCR. Correct PrPpost-translational modifications were confirmed byPNGase-F and Endo-H digestion. We will inoculate ourKIs with CWD-positive material from the correspondingreindeer genotypes [1,2]. The CWD-infected reindeermaterial was characterized by real-time quaking-inducedconversion (RT-QuIC) and its transmissibility to trans-genic mice overexpressing elk PrP (TgElk). Attack rate inthe TgElks were almost 100%, except for those inoculatedwith 138SN lymph node material. Western blotting con-firmed the presence of proteinase-K resistant PrP in allterminally ill mice. Our goal is to analyse the susceptibilityof KIs carrying the 138N allele to intracerebral and per-ipheral prion infection. We will also assess the efficiencyof prion transport from the periphery to the CNS in intraperitoneally inoculated KIs. Prion strain propagationwithin a host is highly dependent on its PrP genotype.This study will provide insight into how the 138N PrPspecifically influences CWD propagation in caribou. 342 - Disease Mechanisms and Model Systems (POF3-342) G:(DE-HGF)POF3-342 POF3-342 POF III 0 Jackson, Walker Scot P:(DE-2719)2810253 1 dzne PERI:(DE-600)2267671-5 28 - 29 Prion 13 2019 1933-6896 https://www.tandfonline.com/doi/pdf/10.1080/19336896.2019.1615197 http://pub.dzne.de/record/145575/files/DZNE-2020-00908.pdf OpenAccess http://pub.dzne.de/record/145575/files/DZNE-2020-00908.pdf?subformat=pdfa pdfa OpenAccess oai:pub.dzne.de:145575 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 0 P:(DE-2719)2810486 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 1 P:(DE-2719)2810253 DE-HGF Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-342 G:(DE-HGF)POF3 G:(DE-HGF)POF3-300 G:(DE-HGF)POF Disease Mechanisms and Model Systems 0 2019 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-18 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2020-01-17 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2022-11-18 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2020-01-17 Creative Commons Attribution CC BY 4.0 LIC:(DE-HGF)CCBY4 HGFVOC JCR StatID:(DE-HGF)0100 StatID PRION : 2021 2022-11-18 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2021-09-28T11:59:09Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2021-09-28T11:59:09Z DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2022-11-18 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2022-11-18 IF < 5 StatID:(DE-HGF)9900 StatID 2022-11-18 OpenAccess StatID:(DE-HGF)0510 StatID Peer Review StatID:(DE-HGF)0030 StatID DOAJ : Blind peer review 2021-09-28T11:59:09Z Article Processing Charges StatID:(DE-HGF)0561 StatID 2020-01-17 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-18 Fees StatID:(DE-HGF)0700 StatID 2020-01-17 I:(DE-2719)1013019 AG Jackson Selective Vulnerability of Neurodegenerative Diseases 0 abstract VDB UNRESTRICTED journal I:(DE-2719)1013019 FullTexts