{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:05:12Z","timestamp":1791291912966,"version":"4.1.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"28","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,7,11]]},"abstract":"<jats:p>\n                    All neuropathologically confirmed cases of variant Creutzfeldt\u2013Jakob disease (vCJD), characterized by abundant florid plaques and type 4 disease-related prion protein (PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    ) in the brain, have been homozygous for methionine at polymorphic residue 129 of\n                    <jats:italic>PRNP<\/jats:italic>\n                    . The distinctive neuropathological and molecular phenotype of vCJD can be faithfully recapitulated in\n                    <jats:italic>Prnp<\/jats:italic>\n                    -null transgenic mice homozygous for human PrP M129 but not V129, where a distinct prion strain is propagated. Here we model susceptibility of 129MV heterozygotes, the most common\n                    <jats:italic>PRNP<\/jats:italic>\n                    genotype, in transgenic mice and show that, remarkably, propagation of type 4 PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    was not associated with characteristic vCJD neuropathology. Depending on the source of the inoculum these mice can develop four distinct disease phenotypes after challenge with bovine spongiform encephalopathy (BSE) prions or vCJD (human-passaged BSE) prions. vCJD-challenged mice had higher attack rates of prion infection than BSE-challenged recipients. These data argue that human\n                    <jats:italic>PRNP<\/jats:italic>\n                    129 heterozygotes will be more susceptible to infection with vCJD prions than to cattle BSE prions and may present with a neuropathological phenotype distinct from vCJD.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0604292103","type":"journal-article","created":{"date-parts":[[2006,6,30]],"date-time":"2006-06-30T06:23:07Z","timestamp":1151648587000},"page":"10759-10764","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":66,"title":["Dissociation of pathological and molecular phenotype of variant Creutzfeldt\u2013Jakob disease in transgenic human prion protein 129 heterozygous mice"],"prefix":"10.1073","volume":"103","author":[{"given":"Emmanuel A.","family":"Asante","sequence":"first","affiliation":[{"name":"Medical Research Council Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline M.","family":"Linehan","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Gowland","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Joiner","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Fox","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Cooper","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olufumilayo","family":"Osiguwa","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Gorry","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Welch","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Houghton","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Desbruslais","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Brandner","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D. F.","family":"Wadsworth","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Collinge","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,7,11]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/2151043a0"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.23.13363"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.24.1.519"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.12.7859-7868.1994"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/383685a0"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410390613"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5295.2079"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg125"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)91412-9"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/38925"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/39057"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf653"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)05128-4"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1580"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17143-2"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)05403-4"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)15486-X"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16811-6"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/352340a0"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)93128-V"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1083320"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1086\/317935"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)92953-Y"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/115.3.675"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/115.3.687"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/9030"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1103932"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2003.10.007"},{"key":"e_1_3_4_29_2","first-page":"1215","volume":"46","author":"Owen F.","year":"1990","unstructured":"F. 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