{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T04:53:20Z","timestamp":1792731200286,"version":"4.5.0"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,4,15]]},"abstract":"<jats:p>\n                    Transgenic (Tg) mouse lines that express chimeric mouse\u2013human prion protein (PrP), designated MHu2M, are susceptible to prions from patients with sporadic Creutzfeldt\u2013Jakob disease (sCJD). With the aim of decreasing the incubation time to fewer than 200 days, we constructed transgenes in which one or more of the nine human residues in MHu2M were changed to mouse. The construct with murine residues at positions 165 and 167 was expressed in Tg(MHu2M,M165V,E167Q) mice and resulted in shortening the incubation time to \u2248110 days for prions from sCJD patients. The construct with a murine residue at position 96 resulted in lengthening the incubation time to more than 280 days for sCJD prions. When murine residues 96, 165, and 167 were expressed, the abbreviated incubation times for sCJD prions were abolished. Variant CJD prions showed prolonged incubation times between 300 and 700 days in Tg(MHu2M) mice on first passage and incubation times of \u2248350 days in Tg(MHu2M,M165V,E167Q) mice. On second and third passages of variant CJD prions in Tg(MHu2M) mice, multiple strains of prions were detected based on incubation times and the sizes of the protease-resistant, deglycosylated PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    fragments. Our discovery of a previously undescribed chimeric transgene with abbreviated incubation times for sCJD prions should facilitate studies on the prion species barrier and human prion diversity.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2627989100","type":"journal-article","created":{"date-parts":[[2003,4,15]],"date-time":"2003-04-15T18:56:03Z","timestamp":1050432963000},"page":"4784-4789","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":117,"title":["Abbreviated incubation times for human prions in mice expressing a chimeric mouse\u2013human prion protein transgene"],"prefix":"10.1073","volume":"100","author":[{"given":"Carsten","family":"Korth","sequence":"first","affiliation":[{"name":"Institute for Neurodegenerative Diseases and Departments of Neurology, Pathology, and Biochemistry and Biophysics, University of California, San Francisco, CA 94143; Division of Neuropathology, Case Western Reserve University, Cleveland, OH 44106; National CJD Surveillance Unit, Western General Hospital, Edinburgh EX4 2HU, United Kingdom; and Neuropathology Laboratory, University of Edinburgh, Edinburgh EH8 9LJ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyotoshi","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Diseases and Departments of Neurology, Pathology, and Biochemistry and Biophysics, University of California, San Francisco, CA 94143; Division of Neuropathology, Case Western Reserve University, Cleveland, OH 44106; National CJD Surveillance Unit, Western General Hospital, Edinburgh EX4 2HU, United Kingdom; and Neuropathology Laboratory, University of Edinburgh, Edinburgh EH8 9LJ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darlene","family":"Groth","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Diseases and Departments of Neurology, Pathology, and Biochemistry and Biophysics, University of California, San Francisco, CA 94143; Division of Neuropathology, Case Western Reserve University, Cleveland, OH 44106; National CJD Surveillance Unit, Western General Hospital, Edinburgh EX4 2HU, United Kingdom; and Neuropathology Laboratory, University of Edinburgh, Edinburgh EH8 9LJ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Heye","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Diseases and Departments of Neurology, Pathology, and Biochemistry and Biophysics, University of California, San Francisco, CA 94143; Division of Neuropathology, Case Western Reserve University, Cleveland, OH 44106; National CJD Surveillance Unit, Western General Hospital, Edinburgh EX4 2HU, United Kingdom; and Neuropathology Laboratory, University of Edinburgh, Edinburgh EH8 9LJ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn","family":"Telling","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Diseases and Departments of Neurology, Pathology, and Biochemistry and Biophysics, University of California, San Francisco, CA 94143; 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Division of Neuropathology, Case Western Reserve University, Cleveland, OH 44106; National CJD Surveillance Unit, Western General Hospital, Edinburgh EX4 2HU, United Kingdom; and Neuropathology Laboratory, University of Edinburgh, Edinburgh EH8 9LJ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Tremblay","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Diseases and Departments of Neurology, Pathology, and Biochemistry and Biophysics, University of California, San Francisco, CA 94143; Division of Neuropathology, Case Western Reserve University, Cleveland, OH 44106; National CJD Surveillance Unit, Western General Hospital, Edinburgh EX4 2HU, United Kingdom; and Neuropathology Laboratory, University of Edinburgh, Edinburgh EH8 9LJ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"DeArmond","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Diseases and Departments of Neurology, Pathology, and Biochemistry and Biophysics, University of California, San Francisco, CA 94143; 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