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dc.contributor.authorFaas, Henryken_US
dc.contributor.authorWatson, Nickien_US
dc.contributor.authorBorkowski, Andrew W.en_US
dc.contributor.authorJasanoff, Alan Pradipen_US
dc.contributor.authorKing, Oliver D.en_US
dc.contributor.authorSteele, Andrew D.en_US
dc.contributor.authorLindquist, Susanen_US
dc.contributor.authorJackson, Walker S.en_US
dc.date.accessioned2009-10-19T13:46:36Z
dc.date.available2009-10-19T13:46:36Z
dc.date.issued2009-08en_US
dc.identifier.issn0896-6273en_US
dc.identifier.urihttp://hdl.handle.net/1721.1/49488
dc.description.abstractA crucial tenet of the prion hypothesis is that misfolding of the prion protein (PrP) induced by mutations associated with familial prion disease is, in an otherwise normal mammalian brain, sufficient to generate the infectious agent. Yet this has never been demonstrated. We engineered knockin mice to express a PrP mutation associated with a distinct human prion disease, fatal familial insomnia (FFI). An additional substitution created a strong transmission barrier against pre-existing prions. The mice spontaneously developed a disease distinct from that of other mouse prion models and highly reminiscent of FFI. Unique pathology was transmitted from FFI mice to mice expressing wild-type PrP sharing the same transmission barrier. FFI mice were highly resistant to infection by pre-existing prions, confirming infectivity did not arise from contaminating agents. Thus, a single amino acid change in PrP is sufficient to induce a distinct neurodegenerative disease and the spontaneous generation of prion infectivity.en_US
dc.language.isoen_USen_US
dc.publisherElsevier Inc.en_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.neuron.2009.07.026en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourceWalker Jacksonen_US
dc.titleSpontaneous generation of prion infectivity in fatal familial insomnia knock-in miceen_US
dc.title.alternativeSpontaneous Generation of Prion Infectivity in Fatal Familial Insomnia Knockin Miceen_US
dc.typeArticleen_US
dc.identifier.citationJackson W.S., Borkowski A.W., Faas H., Steele A.D., King O.D., Watson N., Jasanoff A., Lindquist S. Spontaneous Generation of Prion Infectivity in Fatal Familial Insomnia Knockin Mice (2009) Neuron, 63 (4), pp. 438-450.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciencesen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Nuclear Science and Engineeringen_US
dc.contributor.departmentWhitehead Institute for Biomedical Researchen_US
dc.contributor.departmentFrancis Bitter Magnet Laboratory (Massachusetts Institute of Technology)en_US
dc.contributor.approverJackson, Walker S.en_US
dc.contributor.mitauthorJackson, Walker S.en_US
dc.contributor.mitauthorBorkowski, Andrew W.en_US
dc.contributor.mitauthorSteele, Andrew D.en_US
dc.contributor.mitauthorFaas, Henryken_US
dc.contributor.mitauthorLindquist, Susanen_US
dc.contributor.mitauthorKing, Oliver D.en_US
dc.contributor.mitauthorWatson, Nickien_US
dc.contributor.mitauthorJasanoff, Alan Pradipen_US
dc.relation.journalNeuronen_US
dc.eprint.versionAuthor's final manuscript
dc.type.urihttp://purl.org/eprint/type/SubmittedJournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsJackson, Walker S.; Borkowski, Andrew W.; Faas, Henryk; Steele, Andrew D.; King, Oliver D.; Watson, Nicki; Jasanoff, Alan; Lindquist, Susanen
dc.identifier.orcidhttps://orcid.org/0000-0002-2834-6359
dc.identifier.orcidhttps://orcid.org/0000-0003-1307-882X
mit.licensePUBLISHER_POLICYen_US
mit.metadata.statusComplete


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