{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T12:20:15Z","timestamp":1767356415173,"version":"3.48.0"},"reference-count":8,"publisher":"The Royal Society","issue":"1306","license":[{"start":{"date-parts":[[1994,3,29]],"date-time":"1994-03-29T00:00:00Z","timestamp":764899200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1994,3,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neuropathologic examination of transgenic (Tg) mice which express different prion protein (PrP) constructs is essential because spongiform (vacuolar) degeneration of neurons, the distribution of PrPSc and whether PrP amyloid plaques form are the phenotypes of prion diseases. In Tg models of experimental scrapie, it was found that all of the parameters that define prion isolates (\u2018strains\u2019) can be manipulated by changing the structure of PrP. In those studies, further evidence that PrPSc causes scrapie neuropathology and determines scrapie incubation time was obtained. In addition, the distribution of PrPSc in the brain was unique for each prion isolate. The implications of these findings are first, that prion isolates target different neuron populations for synthesis of nascent pathogenic PrPSc and, secondly, that prion isolate diversity is determined by neurons. In Tg mice which express mutated PrP mimicking human prion protein genemutations linked to familial prion diseases, the neuropathological changes have been faithfully reproduced. A new age-related, neuromascular disorder has also been identified in uninfected Tg mice which overexpress wild-type PrPC . All of the findings with different PrP constructs plus the absence of scrapie pathology in PrP null mice are the strongest argument that the prion protein is the main etiologic and pathogenic factor of prion disorders.<\/jats:p>","DOI":"10.1098\/rstb.1994.0038","type":"journal-article","created":{"date-parts":[[2006,12,15]],"date-time":"2006-12-15T17:54:58Z","timestamp":1166205298000},"page":"415-423","source":"Crossref","is-referenced-by-count":4,"title":["The neuropathological phenotype in transgenic mice expressing different prion protein constructs"],"prefix":"10.1098","volume":"343","author":[{"given":"Stephen J.","family":"DeArmond","sequence":"first","affiliation":[{"name":"Departments of Pathology(Neuropathology), and Neurology, University of California, San Francisco, California 94143, U. S. A."},{"name":"Departments of Pathology(Neuropathology), University of California, San Francisco, California 94143, U. S. A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu Lian","family":"Yang","sequence":"additional","affiliation":[{"name":"Departments of Pathology(Neuropathology), University of California, San Francisco, California 94143, U. S. A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Cayetano-Canlas","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, San Francisco, California 94143, U. S. A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darlene","family":"Groth","sequence":"additional","affiliation":[{"name":"Neurology, and Biochemistry and Biophysics, University of California, San Francisco, California 94143, U. S. A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanley Ben","family":"Prusiner","sequence":"additional","affiliation":[{"name":"Departments of Pathology(Neuropathology), University of California, San Francisco, California 94143, U. S. A."},{"name":"Department of Neurology, University of California, San Francisco, California 94143, U. S. A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"175","reference":[{"key":"p_1","doi-asserted-by":"publisher","DOI":"10.1038\/214764a0"},{"key":"p_2","first-page":"503","article-title":"The scrapie agent: evidence against its d ep en d en ce for rep licatio n on intrinsic nucleic acid. J .gen","volume":"41","author":"Iper A","year":"1978","journal-title":"Virol."},{"key":"p_3","first-page":"159","article-title":"Purified scrapie prions resist in a c tivation by U V irra d ia tio n . J","volume":"61","author":"B","year":"1978","journal-title":"Virol."},{"key":"p_4","unstructured":"B ellin g er-K aw ah ara C. D iener T .O . M cK inley M .P . G row th D .F . S m ith D .R . & P rusiner S.B. 19876"},{"key":"p_5","unstructured":"(P alm er et al.1991; Brown et al. 1992; C ollinge et"},{"key":"p_6","unstructured":"Purified scrapie prions resist in activ atio n by procedures"},{"key":"p_7","unstructured":"al. 1992)."},{"key":"p_8","unstructured":"C O N C L U D I N G R E M A R K S"}],"container-title":["Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rstb.1994.0038","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/rstb\/article-pdf\/343\/1306\/415\/83166\/rstb.1994.0038.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/royalsocietypublishing.org\/rstb\/article-pdf\/343\/1306\/415\/83166\/rstb.1994.0038.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T12:17:22Z","timestamp":1767356242000},"score":1,"resource":{"primary":{"URL":"https:\/\/royalsocietypublishing.org\/rstb\/article\/343\/1306\/415\/18563\/The-neuropathological-phenotype-in-transgenic-mice"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,3,29]]},"references-count":8,"journal-issue":{"issue":"1306","published-print":{"date-parts":[[1994,3,29]]}},"URL":"https:\/\/doi.org\/10.1098\/rstb.1994.0038","relation":{},"ISSN":["0962-8436","1471-2970"],"issn-type":[{"type":"print","value":"0962-8436"},{"type":"electronic","value":"1471-2970"}],"subject":[],"published":{"date-parts":[[1994,3,29]]}}}