Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication
Transgenic (Tg) mice expressing both Syrian hamster (Ha) and mouse (Mo) prion protein (PrP) genes were used to probe the mechanism of scrapie prion replication. Four Tg lines expressing HaPrP exhibited distinct incubation times ranging from 48 to 277 days, which correlated inversely with HaPrP mRNA...
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| Veröffentlicht in: | Cell 1990-11, Vol.63 (4), p.673-686 |
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| container_title | Cell |
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| creator | Prusiner, Stanley B. Scott, Michael Foster, Dallas Pan, Keh-Ming Groth, Darlene Mirenda, Carol Torchia, Marilyn Yang, Shu-Lian Serban, Dan Carlson, George A. Hoppe, Peter C. Westaway, David DeArmond, Stephen J. |
| description | Transgenic (Tg) mice expressing both Syrian hamster (Ha) and mouse (Mo) prion protein (PrP) genes were used to probe the mechanism of scrapie prion replication. Four Tg lines expressing HaPrP exhibited distinct incubation times ranging from 48 to 277 days, which correlated inversely with HaPrP mRNA and HaPrP
C. Bioassays of Tg brain extracts showed that the prion inoculum dictates which prions are synthesized de novo. Tg mice inoculated with Ha prions had ∼10
9 ID
50 units of Ha prions per gram of brain and |
| doi_str_mv | 10.1016/0092-8674(90)90134-Z |
| format | Article |
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C. Bioassays of Tg brain extracts showed that the prion inoculum dictates which prions are synthesized de novo. Tg mice inoculated with Ha prions had ∼10
9 ID
50 units of Ha prions per gram of brain and <10 units of Mo prions. Conversely, Tg mice inoculated with Mo prions synthesized Mo prions but not Ha prions. Similarly, Tg mice inoculated with Ha prions exhibited neuropathologic changes characteristic of hamsters with scrapie, while Mo prions produced changes similar to those in non-Tg mice. Our results argue that species specificity of scrapie prions resides in the PrP sequence and prion synthesis is initiated by a species-specific interaction between PrP
Sc in the inoculum and homologous PrP
C.</description><identifier>ISSN: 0092-8674</identifier><identifier>EISSN: 1097-4172</identifier><identifier>DOI: 10.1016/0092-8674(90)90134-Z</identifier><identifier>PMID: 1977523</identifier><identifier>CODEN: CELLB5</identifier><language>eng</language><publisher>Cambridge, MA: Elsevier Inc</publisher><subject>Animals ; Biological and medical sciences ; Blotting, Northern ; Blotting, Western ; Brain - metabolism ; Brain - microbiology ; Brain - pathology ; Cricetinae ; Enzyme-Linked Immunosorbent Assay ; Fundamental and applied biological sciences. Psychology ; Mesocricetus ; Mice ; Mice, Transgenic ; Molecular and cellular biology ; Molecular genetics ; Nerve Degeneration ; Prions - genetics ; Prions - physiology ; PrPSc Proteins ; Replication ; RNA, Messenger - genetics ; Transcription, Genetic ; Viral Proteins - genetics ; Virus Replication</subject><ispartof>Cell, 1990-11, Vol.63 (4), p.673-686</ispartof><rights>1990</rights><rights>1991 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c535t-fbfb2a7e96930416880368cbe7c980279094ca07da12b97ec6d27caf175ea65f3</citedby><cites>FETCH-LOGICAL-c535t-fbfb2a7e96930416880368cbe7c980279094ca07da12b97ec6d27caf175ea65f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/0092-8674(90)90134-Z$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19385554$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1977523$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Prusiner, Stanley B.</creatorcontrib><creatorcontrib>Scott, Michael</creatorcontrib><creatorcontrib>Foster, Dallas</creatorcontrib><creatorcontrib>Pan, Keh-Ming</creatorcontrib><creatorcontrib>Groth, Darlene</creatorcontrib><creatorcontrib>Mirenda, Carol</creatorcontrib><creatorcontrib>Torchia, Marilyn</creatorcontrib><creatorcontrib>Yang, Shu-Lian</creatorcontrib><creatorcontrib>Serban, Dan</creatorcontrib><creatorcontrib>Carlson, George A.</creatorcontrib><creatorcontrib>Hoppe, Peter C.</creatorcontrib><creatorcontrib>Westaway, David</creatorcontrib><creatorcontrib>DeArmond, Stephen J.</creatorcontrib><title>Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication</title><title>Cell</title><addtitle>Cell</addtitle><description>Transgenic (Tg) mice expressing both Syrian hamster (Ha) and mouse (Mo) prion protein (PrP) genes were used to probe the mechanism of scrapie prion replication. Four Tg lines expressing HaPrP exhibited distinct incubation times ranging from 48 to 277 days, which correlated inversely with HaPrP mRNA and HaPrP
C. Bioassays of Tg brain extracts showed that the prion inoculum dictates which prions are synthesized de novo. Tg mice inoculated with Ha prions had ∼10
9 ID
50 units of Ha prions per gram of brain and <10 units of Mo prions. Conversely, Tg mice inoculated with Mo prions synthesized Mo prions but not Ha prions. Similarly, Tg mice inoculated with Ha prions exhibited neuropathologic changes characteristic of hamsters with scrapie, while Mo prions produced changes similar to those in non-Tg mice. Our results argue that species specificity of scrapie prions resides in the PrP sequence and prion synthesis is initiated by a species-specific interaction between PrP
Sc in the inoculum and homologous PrP
C.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blotting, Northern</subject><subject>Blotting, Western</subject><subject>Brain - metabolism</subject><subject>Brain - microbiology</subject><subject>Brain - pathology</subject><subject>Cricetinae</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Mesocricetus</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Molecular and cellular biology</subject><subject>Molecular genetics</subject><subject>Nerve Degeneration</subject><subject>Prions - genetics</subject><subject>Prions - physiology</subject><subject>PrPSc Proteins</subject><subject>Replication</subject><subject>RNA, Messenger - genetics</subject><subject>Transcription, Genetic</subject><subject>Viral Proteins - genetics</subject><subject>Virus Replication</subject><issn>0092-8674</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFP3DAQha2qiC60_6CVfClqD6HjJI7jS6UKlYKEBAd64WI5zgSMknjxeFvx7-slq5ZTOdnSfO9p5j3G3gs4FiCaLwC6LNpG1Z80fNYgqrq4ecVWArQqaqHK12z1F3nDDojuAaCVUu6zfaGVkmW1YnfX0c50izMm7zilTe-RuJ_Wo3c2Ifdzwmhd8mEm3mH6jTjzuzCFMdyGDfGreMU9hSHEKctmTi7atUe-jlnBIy4--f-W7Q12JHy3ew_Zz9Pv1ydnxcXlj_OTbxeFk5VMxdANXWkV6kZXUIumbaFqWtehcrqFUmnQtbOgeivKTit0TV8qZwehJNpGDtUhO1p81zE8bJCSmTw5HEc7Y17YtABKQE7rJVDIVueVqgzWC-hiIIo4mHzcZOOjEWC2TZhtzGYbs9FgnpowN1n2Yee_6Sbs_4mW6PP8425uydlxyD04T8-wattVnbmvC4c5tV8eoyHncXbY-4gumT74_y_yBxqepxc</recordid><startdate>19901116</startdate><enddate>19901116</enddate><creator>Prusiner, Stanley B.</creator><creator>Scott, Michael</creator><creator>Foster, Dallas</creator><creator>Pan, Keh-Ming</creator><creator>Groth, Darlene</creator><creator>Mirenda, Carol</creator><creator>Torchia, Marilyn</creator><creator>Yang, Shu-Lian</creator><creator>Serban, Dan</creator><creator>Carlson, George A.</creator><creator>Hoppe, Peter C.</creator><creator>Westaway, David</creator><creator>DeArmond, Stephen J.</creator><general>Elsevier Inc</general><general>Cell Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>19901116</creationdate><title>Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication</title><author>Prusiner, Stanley B. ; Scott, Michael ; Foster, Dallas ; Pan, Keh-Ming ; Groth, Darlene ; Mirenda, Carol ; Torchia, Marilyn ; Yang, Shu-Lian ; Serban, Dan ; Carlson, George A. ; Hoppe, Peter C. ; Westaway, David ; DeArmond, Stephen J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c535t-fbfb2a7e96930416880368cbe7c980279094ca07da12b97ec6d27caf175ea65f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blotting, Northern</topic><topic>Blotting, Western</topic><topic>Brain - metabolism</topic><topic>Brain - microbiology</topic><topic>Brain - pathology</topic><topic>Cricetinae</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Mesocricetus</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Molecular and cellular biology</topic><topic>Molecular genetics</topic><topic>Nerve Degeneration</topic><topic>Prions - genetics</topic><topic>Prions - physiology</topic><topic>PrPSc Proteins</topic><topic>Replication</topic><topic>RNA, Messenger - genetics</topic><topic>Transcription, Genetic</topic><topic>Viral Proteins - genetics</topic><topic>Virus Replication</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Prusiner, Stanley B.</creatorcontrib><creatorcontrib>Scott, Michael</creatorcontrib><creatorcontrib>Foster, Dallas</creatorcontrib><creatorcontrib>Pan, Keh-Ming</creatorcontrib><creatorcontrib>Groth, Darlene</creatorcontrib><creatorcontrib>Mirenda, Carol</creatorcontrib><creatorcontrib>Torchia, Marilyn</creatorcontrib><creatorcontrib>Yang, Shu-Lian</creatorcontrib><creatorcontrib>Serban, Dan</creatorcontrib><creatorcontrib>Carlson, George A.</creatorcontrib><creatorcontrib>Hoppe, Peter C.</creatorcontrib><creatorcontrib>Westaway, David</creatorcontrib><creatorcontrib>DeArmond, Stephen J.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Prusiner, Stanley B.</au><au>Scott, Michael</au><au>Foster, Dallas</au><au>Pan, Keh-Ming</au><au>Groth, Darlene</au><au>Mirenda, Carol</au><au>Torchia, Marilyn</au><au>Yang, Shu-Lian</au><au>Serban, Dan</au><au>Carlson, George A.</au><au>Hoppe, Peter C.</au><au>Westaway, David</au><au>DeArmond, Stephen J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>1990-11-16</date><risdate>1990</risdate><volume>63</volume><issue>4</issue><spage>673</spage><epage>686</epage><pages>673-686</pages><issn>0092-8674</issn><eissn>1097-4172</eissn><coden>CELLB5</coden><abstract>Transgenic (Tg) mice expressing both Syrian hamster (Ha) and mouse (Mo) prion protein (PrP) genes were used to probe the mechanism of scrapie prion replication. Four Tg lines expressing HaPrP exhibited distinct incubation times ranging from 48 to 277 days, which correlated inversely with HaPrP mRNA and HaPrP
C. Bioassays of Tg brain extracts showed that the prion inoculum dictates which prions are synthesized de novo. Tg mice inoculated with Ha prions had ∼10
9 ID
50 units of Ha prions per gram of brain and <10 units of Mo prions. Conversely, Tg mice inoculated with Mo prions synthesized Mo prions but not Ha prions. Similarly, Tg mice inoculated with Ha prions exhibited neuropathologic changes characteristic of hamsters with scrapie, while Mo prions produced changes similar to those in non-Tg mice. Our results argue that species specificity of scrapie prions resides in the PrP sequence and prion synthesis is initiated by a species-specific interaction between PrP
Sc in the inoculum and homologous PrP
C.</abstract><cop>Cambridge, MA</cop><pub>Elsevier Inc</pub><pmid>1977523</pmid><doi>10.1016/0092-8674(90)90134-Z</doi><tpages>14</tpages></addata></record> |
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| ispartof | Cell, 1990-11, Vol.63 (4), p.673-686 |
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| subjects | Animals Biological and medical sciences Blotting, Northern Blotting, Western Brain - metabolism Brain - microbiology Brain - pathology Cricetinae Enzyme-Linked Immunosorbent Assay Fundamental and applied biological sciences. Psychology Mesocricetus Mice Mice, Transgenic Molecular and cellular biology Molecular genetics Nerve Degeneration Prions - genetics Prions - physiology PrPSc Proteins Replication RNA, Messenger - genetics Transcription, Genetic Viral Proteins - genetics Virus Replication |
| title | Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication |
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