{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T11:10:04Z","timestamp":1761217804230,"version":"3.37.3"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,8,25]],"date-time":"2015-08-25T00:00:00Z","timestamp":1440460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG021601"],"award-info":[{"award-number":["AG021601"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG002132"],"award-info":[{"award-number":["AG002132"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG010770"],"award-info":[{"award-number":["AG010770"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG042453"],"award-info":[{"award-number":["AG042453"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG031189"],"award-info":[{"award-number":["AG031189"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fight for Mike Program","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"DOI":"10.13039\/100011756","name":"Sherman Fairchild Foundation","doi-asserted-by":"crossref","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100011756","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Mutations in the gene encoding the prion protein (PrP) are responsible for approximately 10 to 15% of cases of prion disease in humans, including Creutzfeldt\u2010Jakob disease (CJD). Here, we report on the discovery of a previously unreported C\u2010terminal PrP mutation (A224V) in a CJD patient exhibiting a disease similar to the rare VV1 subtype of sporadic (s) CJD and investigate the role of this mutation in prion replication and transmission.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We generated transgenic (Tg) mice expressing human PrP with the V129 polymorphism and A224V mutation, denoted Tg(HuPrP,V129,A224V) mice, and inoculated them with different subtypes of sCJD prions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Transmission of sCJD VV2 or MV2 prions was accelerated in Tg(HuPrP,V129,A224V) mice, compared to Tg(HuPrP,V129) mice, with incubation periods of \u223c110 and \u223c210 days, respectively. In contrast, sCJD MM1 prions resulted in longer incubation periods in Tg(HuPrP,V129,A224V) mice, compared to Tg(HuPrP,V129) mice (\u223c320 vs. \u223c210 days). Prion strain fidelity was maintained in Tg(HuPrP,V129,A224V) mice inoculated with sCJD VV2 or MM1 prions, despite the altered replication kinetics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our results suggest that A224V is a risk factor for prion disease and modulates the transmission behavior of CJD prions in a strain\u2010specific manner, arguing that residues near the C\u2010terminus of PrP are important for controlling the kinetics of prion replication. Ann Neurol 2015;78:540\u2013553<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.24463","type":"journal-article","created":{"date-parts":[[2015,6,20]],"date-time":"2015-06-20T08:52:56Z","timestamp":1434790376000},"page":"540-553","source":"Crossref","is-referenced-by-count":19,"title":["Modulation of <scp>C<\/scp>reutzfeldt\u2010<scp>J<\/scp>akob disease prion propagation by the <scp>A<\/scp>224<scp>V<\/scp> mutation"],"prefix":"10.1002","volume":"78","author":[{"given":"Joel C.","family":"Watts","sequence":"first","affiliation":[{"name":"Institute for Neurodegenerative Diseases"},{"name":"Departments of Neurology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kurt","family":"Giles","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Diseases"},{"name":"Departments of Neurology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Serban","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Smita","family":"Patel","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abby","family":"Oehler","sequence":"additional","affiliation":[{"name":"Pathology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumita","family":"Bhardwaj","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shenheng","family":"Guan","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Diseases"},{"name":"Pharmaceutical Chemistry"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael D.","family":"Greicius","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences Stanford University Stanford CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce L.","family":"Miller","sequence":"additional","affiliation":[{"name":"Memory and Aging Center"},{"name":"Departments of Neurology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen J.","family":"DeArmond","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Diseases"},{"name":"Pathology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael D.","family":"Geschwind","sequence":"additional","affiliation":[{"name":"Memory and Aging Center"},{"name":"Departments of Neurology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanley B.","family":"Prusiner","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Diseases"},{"name":"Departments of Neurology"},{"name":"Biochemistry and Biophysics University of California San Francisco San Francisco CA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,8,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006833"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(83)90207-6"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199908)46:2<224::AID-ANA12>3.0.CO;2-W"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/375698a0"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5295.2079"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0585-1"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl159"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2627989100"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1004688107"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1317164110"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/356577a0"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1121556109"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902930"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt748"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90236-8"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003990"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)90118-3"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.2.192"},{"key":"e_1_2_8_20_1","first-page":"1551","article-title":"Diffusion\u2010weighted and fluid\u2010attenuated inversion recovery imaging in Creutzfeldt\u2010Jakob disease: high sensitivity and specificity for diagnosis","volume":"26","author":"Young GS","year":"2005","journal-title":"Am J Neuroradiol"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31821a4439"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90177-5"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf653"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-007-0540-9"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21281"},{"key":"e_1_2_8_26_1","unstructured":"Exome Aggregation Consortium (ExAC). Cambridge MA: Broad Institute 2014. Available at:http:\/\/exac.broadinstitute.org. Accessed November 25 2014."},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410340608"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401601"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1237758"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/352340a0"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21358"},{"key":"e_1_2_8_32_1","first-page":"673","volume-title":"Cold Spring Harbor","author":"Kong Q","year":"2004"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020012"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000184674.32924.c9"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2008.09.017"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R114.550707"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1312006110"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002350"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.007930-0"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1980379"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.14.1736"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600717"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.07027-11"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.23.6855"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.1.145"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0609-x"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000666"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1204498109"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(87)90063-7"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-110711-155524"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.24463","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.24463","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T14:02:12Z","timestamp":1696600932000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.24463"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,25]]},"references-count":49,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2015,10]]}},"alternative-id":["10.1002\/ana.24463"],"URL":"https:\/\/doi.org\/10.1002\/ana.24463","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"type":"print","value":"0364-5134"},{"type":"electronic","value":"1531-8249"}],"subject":[],"published":{"date-parts":[[2015,8,25]]}}}