{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:07:44Z","timestamp":1791328064499,"version":"4.3.1"},"reference-count":23,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5702","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2004,12,3]]},"abstract":"<jats:p>Variant Creutzfeldt-Jakob disease (vCJD) is a unique and highly distinctive clinicopathological and molecular phenotype of human prion disease associated with infection with bovine spongiform encephalopathy (BSE)\u2013like prions. Here, we found that generation of this phenotype in transgenic mice required expression of human prion protein (PrP) with methionine 129. Expression of human PrP with valine 129 resulted in a distinct phenotype and, remarkably, persistence of a barrier to transmission of BSE-derived prions on subpassage. Polymorphic residue 129 of human PrP dictated propagation of distinct prion strains after BSE prion infection. Thus, primary and secondary human infection with BSE-derived prions may result in sporadic CJD-like or novel phenotypes in addition to vCJD, depending on the genotype of the prion source and the recipient.<\/jats:p>","DOI":"10.1126\/science.1103932","type":"journal-article","created":{"date-parts":[[2004,11,11]],"date-time":"2004-11-11T20:24:44Z","timestamp":1100204684000},"page":"1793-1796","source":"Crossref","is-referenced-by-count":230,"title":["Human Prion Protein with Valine 129 Prevents Expression of Variant CJD Phenotype"],"prefix":"10.1126","volume":"306","author":[{"given":"Jonathan D. F.","family":"Wadsworth","sequence":"first","affiliation":[{"name":"Medical Research Council (MRC) Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel A.","family":"Asante","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Desbruslais","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline M.","family":"Linehan","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Joiner","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Gowland","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Welch","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Stone","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Lloyd","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew F.","family":"Hill","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Brandner","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Collinge","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/383685a0"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/9030"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg125"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)93128-V"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/352340a0"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/317935"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1083320"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/378779a0"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/38925"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf653"},{"key":"e_1_3_2_12_2","unstructured":"Materials and methods are available as supporting material on Science Online."},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)91412-9"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.1994.0036"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.041490898"},{"key":"e_1_3_2_16_2","unstructured":"E. A. Asante J. D. F. Wadsworth J. Collinge unpublished observations. These data will be reported in full elsewhere."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)05403-4"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)05128-4"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.24.1.519"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2003.10.007"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M313762200"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)15486-X"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16811-6"},{"key":"e_1_3_2_24_2","unstructured":"We thank C. Brown and his team for animal care R. Young for preparation of figures and K. Fox and S. Cooper for technical assistance. We especially thank all patients and their families for generously consenting to use of human tissues in this research and the UK neuropathologists who have kindly helped in providing these tissues. We thank R. Bradley D. Matthews S. A. C. Hawkins and colleagues at the UK Veterinary Laboratories Agency for providing BSE tissues. This work was funded by the UK Medical Research Council and European Commission. One of the routine antibodies used in this work (ICSM 35) is marketed by D-Gen Ltd. an academic spin-off company. J.C. is a director of D-Gen and J.C. J.D.F.W. and A.F.H. are shareholders and consultants of D-Gen."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1103932","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T23:29:23Z","timestamp":1704842963000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1103932"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,12,3]]},"references-count":23,"journal-issue":{"issue":"5702","published-print":{"date-parts":[[2004,12,3]]}},"alternative-id":["10.1126\/science.1103932"],"URL":"https:\/\/doi.org\/10.1126\/science.1103932","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1022784.261687","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,12,3]]}}}