{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:14:09Z","timestamp":1791000849217,"version":"4.1.0"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"JSPS KAKENHI","award":["26293212"],"award-info":[{"award-number":["26293212"]}]},{"name":"MEXT KAKENHI","award":["15H01560"],"award-info":[{"award-number":["15H01560"]}]},{"name":"MEXT KAKENHI","award":["17H05701"],"award-info":[{"award-number":["17H05701"]}]},{"name":"Practical Research Project for Rare\/Intractable Diseases of the Japan Agency for Medical Research and Development"},{"name":"JSPS KAKENHI","award":["25870479"],"award-info":[{"award-number":["25870479"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Conformational conversion of the cellular isoform of prion protein, PrP\n            <jats:sup>C<\/jats:sup>\n            , into the abnormally folded, amyloidogenic isoform, PrP\n            <jats:sup>Sc<\/jats:sup>\n            , is a key pathogenic event in prion diseases, including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy (BSE) in animals. We previously reported that the octapeptide repeat (OR) region could be dispensable for converting PrP\n            <jats:sup>C<\/jats:sup>\n            into PrP\n            <jats:sup>Sc<\/jats:sup>\n            after infection with RML prions. We demonstrated that mice transgenically expressing mouse PrP with deletion of the OR region on the PrP knockout background, designated Tg(PrP\u0394OR)\/\n            <jats:italic>\n              Prnp\n              <jats:sup>0<\/jats:sup>\n            <\/jats:italic>\n            <jats:sup>\n              \/\n              <jats:italic>0<\/jats:italic>\n            <\/jats:sup>\n            mice, did not show reduced susceptibility to RML scrapie prions, with abundant accumulation of PrP\n            <jats:sup>Sc<\/jats:sup>\n            \u0394OR in their brains. We show here that Tg(PrP\u0394OR)\/\n            <jats:italic>\n              Prnp\n              <jats:sup>0<\/jats:sup>\n            <\/jats:italic>\n            <jats:sup>\n              \/\n              <jats:italic>0<\/jats:italic>\n            <\/jats:sup>\n            mice were highly resistant to BSE prions, developing the disease with markedly elongated incubation times after infection with BSE prions. The conversion of PrP\u0394OR into PrP\n            <jats:sup>Sc<\/jats:sup>\n            \u0394OR was markedly delayed in their brains. These results suggest that the OR region may have a crucial role in the conversion of PrP\n            <jats:sup>C<\/jats:sup>\n            into PrP\n            <jats:sup>Sc<\/jats:sup>\n            after infection with BSE prions. However, Tg(PrP\u0394OR)\/\n            <jats:italic>\n              Prnp\n              <jats:sup>0<\/jats:sup>\n            <\/jats:italic>\n            <jats:sup>\n              \/\n              <jats:italic>0<\/jats:italic>\n            <\/jats:sup>\n            mice remained susceptible to RML and 22L scrapie prions, developing the disease without elongated incubation times after infection with RML and 22L prions. PrP\n            <jats:sup>Sc<\/jats:sup>\n            \u0394OR accumulated only slightly less in the brains of RML- or 22L-infected Tg(PrP\u0394OR)\/\n            <jats:italic>\n              Prnp\n              <jats:sup>0<\/jats:sup>\n            <\/jats:italic>\n            <jats:sup>\n              \/\n              <jats:italic>0<\/jats:italic>\n            <\/jats:sup>\n            mice than PrP\n            <jats:sup>Sc<\/jats:sup>\n            in control wild-type mice. Taken together, these results indicate that the OR region of PrP\n            <jats:sup>C<\/jats:sup>\n            could play a differential role in the pathogenesis of BSE prions and RML or 22L scrapie prions.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Structure-function relationship studies of PrP\n            <jats:sup>C<\/jats:sup>\n            conformational conversion into PrP\n            <jats:sup>Sc<\/jats:sup>\n            are worthwhile to understand the mechanism of the conversion of PrP\n            <jats:sup>C<\/jats:sup>\n            into PrP\n            <jats:sup>Sc<\/jats:sup>\n            . We show here that, by inoculating Tg(PrP\u0394OR)\/\n            <jats:italic>\n              Prnp\n              <jats:sup>0<\/jats:sup>\n            <\/jats:italic>\n            <jats:sup>\n              \/\n              <jats:italic>0<\/jats:italic>\n            <\/jats:sup>\n            mice with the three different strains of RML, 22L, and BSE prions, the OR region could play a differential role in the conversion of PrP\n            <jats:sup>C<\/jats:sup>\n            into PrP\n            <jats:sup>Sc<\/jats:sup>\n            after infection with RML or 22L scrapie prions and BSE prions. PrP\u0394OR was efficiently converted into PrP\n            <jats:sup>Sc<\/jats:sup>\n            \u0394OR after infection with RML and 22L prions. However, the conversion of PrP\u0394OR into PrP\n            <jats:sup>Sc<\/jats:sup>\n            \u0394OR was markedly delayed after infection with BSE prions. Further investigation into the role of the OR region in the conversion of PrP\n            <jats:sup>C<\/jats:sup>\n            into PrP\n            <jats:sup>Sc<\/jats:sup>\n            after infection with BSE prions might be helpful for understanding the pathogenesis of BSE prions.\n          <\/jats:p>","DOI":"10.1128\/jvi.01368-17","type":"journal-article","created":{"date-parts":[[2017,10,19]],"date-time":"2017-10-19T00:25:30Z","timestamp":1508372730000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Prion Protein Devoid of the Octapeptide Repeat Region Delays Bovine Spongiform Encephalopathy Pathogenesis in Mice"],"prefix":"10.1128","volume":"92","author":[{"given":"Hideyuki","family":"Hara","sequence":"first","affiliation":[{"name":"Division of Molecular Neurobiology, The Institute for Enzyme Research (KOSOKEN), Tokushima University, Kuramoto, Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Miyata","sequence":"additional","affiliation":[{"name":"Animal Research Center, School of Medicine, University of Occupational and Environmental Health, Yahatanishi, Kitakyushu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nandita Rani","family":"Das","sequence":"additional","affiliation":[{"name":"Division of Molecular Neurobiology, The Institute for Enzyme Research (KOSOKEN), Tokushima University, Kuramoto, Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junji","family":"Chida","sequence":"additional","affiliation":[{"name":"Division of Molecular Neurobiology, The Institute for Enzyme Research (KOSOKEN), Tokushima University, Kuramoto, Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatenobu","family":"Yoshimochi","sequence":"additional","affiliation":[{"name":"Division of Molecular Neurobiology, The Institute for Enzyme Research (KOSOKEN), Tokushima University, Kuramoto, Tokushima, Japan"},{"name":"Student Laboratory, Faculty of Medicine, Tokushima University, Kuramoto, Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiji","family":"Uchiyama","sequence":"additional","affiliation":[{"name":"Division of Molecular Neurobiology, The Institute for Enzyme Research (KOSOKEN), Tokushima University, Kuramoto, Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitomi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Biological Science, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gen","family":"Kondoh","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Biological Science, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"National Institute of Animal Health (NIAH), National Agriculture and Food Research Organization (NARO), Tsukuba, Ibaraki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suehiro","family":"Sakaguchi","sequence":"additional","affiliation":[{"name":"Division of Molecular Neurobiology, The Institute for Enzyme Research (KOSOKEN), Tokushima University, Kuramoto, Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.23.13363"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90150-4"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90360-3"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.22.10608"},{"key":"e_1_3_2_6_2","first-page":"331","article-title":"PrP gene dosage determines the timing but not the final intensity or distribution of lesions in scrapie pathology","volume":"3","author":"Manson JC","year":"1994","unstructured":"Manson JC, Clarke AR, McBride PA, McConnell I, Hope J. 1994. 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