A mouse knockout library for secreted and transmembrane proteins
Tang et al . present the first large-scale, gene-specific library of knockout mice. They disrupt 472 genes encoding secreted or transmembrane proteins and report the results of a comprehensive phenotypic analysis. Large collections of knockout organisms facilitate the elucidation of gene functions....
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Veröffentlicht in: | Nature biotechnology 2010-07, Vol.28 (7), p.749-755 |
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creator | Tang, Tracy Li, Li Tang, Jerry Li, Yun Lin, Wei Yu Martin, Flavius Grant, Deanna Solloway, Mark Parker, Leon Ye, Weilan Forrest, William Ghilardi, Nico Oravecz, Tamas Platt, Kenneth A Rice, Dennis S Hansen, Gwenn M Abuin, Alejandro Eberhart, Derek E Godowski, Paul Holt, Kathleen H Peterson, Andrew Zambrowicz, Brian P de Sauvage, Frederic J |
description | Tang
et al
. present the first large-scale, gene-specific library of knockout mice. They disrupt 472 genes encoding secreted or transmembrane proteins and report the results of a comprehensive phenotypic analysis.
Large collections of knockout organisms facilitate the elucidation of gene functions. Here we used retroviral insertion or homologous recombination to disrupt 472 genes encoding secreted and membrane proteins in mice, providing a resource for studying a large fraction of this important class of drug target. The knockout mice were subjected to a systematic phenotypic screen designed to uncover alterations in embryonic development, metabolism, the immune system, the nervous system and the cardiovascular system. The majority of knockout lines exhibited altered phenotypes in at least one of these therapeutic areas. To our knowledge, a comprehensive phenotypic assessment of a large number of mouse mutants generated by a gene-specific approach has not been described previously. |
doi_str_mv | 10.1038/nbt.1644 |
format | Article |
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et al
. present the first large-scale, gene-specific library of knockout mice. They disrupt 472 genes encoding secreted or transmembrane proteins and report the results of a comprehensive phenotypic analysis.
Large collections of knockout organisms facilitate the elucidation of gene functions. Here we used retroviral insertion or homologous recombination to disrupt 472 genes encoding secreted and membrane proteins in mice, providing a resource for studying a large fraction of this important class of drug target. The knockout mice were subjected to a systematic phenotypic screen designed to uncover alterations in embryonic development, metabolism, the immune system, the nervous system and the cardiovascular system. The majority of knockout lines exhibited altered phenotypes in at least one of these therapeutic areas. To our knowledge, a comprehensive phenotypic assessment of a large number of mouse mutants generated by a gene-specific approach has not been described previously.</description><identifier>ISSN: 1087-0156</identifier><identifier>EISSN: 1546-1696</identifier><identifier>DOI: 10.1038/nbt.1644</identifier><identifier>PMID: 20562862</identifier><identifier>CODEN: NABIF9</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/1647/666/2262 ; 631/61/17/1511 ; 631/61/191 ; Agriculture ; Animals ; Bioinformatics ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedical Engineering/Biotechnology ; Biomedicine ; Biotechnology ; Cardiovascular system ; Diverse techniques ; Embryonic development ; Embryonic growth stage ; Fundamental and applied biological sciences. Psychology ; Genetically modified organisms ; Health aspects ; Immune system ; Life Sciences ; Membrane proteins ; Membrane Proteins - genetics ; Membranes ; Methods ; Mice ; Mice, Knockout ; Molecular and cellular biology ; Properties ; Proteins ; resource ; Rodents</subject><ispartof>Nature biotechnology, 2010-07, Vol.28 (7), p.749-755</ispartof><rights>Springer Nature America, Inc. 2010</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2010 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jul 2010</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c643t-f99dea21d63f5baa60b87226bde1d1e4497b6dca451bb75bd8061c203033b8c93</citedby><cites>FETCH-LOGICAL-c643t-f99dea21d63f5baa60b87226bde1d1e4497b6dca451bb75bd8061c203033b8c93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nbt.1644$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nbt.1644$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23019295$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20562862$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tang, Tracy</creatorcontrib><creatorcontrib>Li, Li</creatorcontrib><creatorcontrib>Tang, Jerry</creatorcontrib><creatorcontrib>Li, Yun</creatorcontrib><creatorcontrib>Lin, Wei Yu</creatorcontrib><creatorcontrib>Martin, Flavius</creatorcontrib><creatorcontrib>Grant, Deanna</creatorcontrib><creatorcontrib>Solloway, Mark</creatorcontrib><creatorcontrib>Parker, Leon</creatorcontrib><creatorcontrib>Ye, Weilan</creatorcontrib><creatorcontrib>Forrest, William</creatorcontrib><creatorcontrib>Ghilardi, Nico</creatorcontrib><creatorcontrib>Oravecz, Tamas</creatorcontrib><creatorcontrib>Platt, Kenneth A</creatorcontrib><creatorcontrib>Rice, Dennis S</creatorcontrib><creatorcontrib>Hansen, Gwenn M</creatorcontrib><creatorcontrib>Abuin, Alejandro</creatorcontrib><creatorcontrib>Eberhart, Derek E</creatorcontrib><creatorcontrib>Godowski, Paul</creatorcontrib><creatorcontrib>Holt, Kathleen H</creatorcontrib><creatorcontrib>Peterson, Andrew</creatorcontrib><creatorcontrib>Zambrowicz, Brian P</creatorcontrib><creatorcontrib>de Sauvage, Frederic J</creatorcontrib><title>A mouse knockout library for secreted and transmembrane proteins</title><title>Nature biotechnology</title><addtitle>Nat Biotechnol</addtitle><addtitle>Nat Biotechnol</addtitle><description>Tang
et al
. present the first large-scale, gene-specific library of knockout mice. They disrupt 472 genes encoding secreted or transmembrane proteins and report the results of a comprehensive phenotypic analysis.
Large collections of knockout organisms facilitate the elucidation of gene functions. Here we used retroviral insertion or homologous recombination to disrupt 472 genes encoding secreted and membrane proteins in mice, providing a resource for studying a large fraction of this important class of drug target. The knockout mice were subjected to a systematic phenotypic screen designed to uncover alterations in embryonic development, metabolism, the immune system, the nervous system and the cardiovascular system. The majority of knockout lines exhibited altered phenotypes in at least one of these therapeutic areas. To our knowledge, a comprehensive phenotypic assessment of a large number of mouse mutants generated by a gene-specific approach has not been described previously.</description><subject>631/1647/666/2262</subject><subject>631/61/17/1511</subject><subject>631/61/191</subject><subject>Agriculture</subject><subject>Animals</subject><subject>Bioinformatics</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering/Biotechnology</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>Cardiovascular system</subject><subject>Diverse techniques</subject><subject>Embryonic development</subject><subject>Embryonic growth stage</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetically modified organisms</subject><subject>Health aspects</subject><subject>Immune system</subject><subject>Life Sciences</subject><subject>Membrane proteins</subject><subject>Membrane Proteins - genetics</subject><subject>Membranes</subject><subject>Methods</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Molecular and cellular biology</subject><subject>Properties</subject><subject>Proteins</subject><subject>resource</subject><subject>Rodents</subject><issn>1087-0156</issn><issn>1546-1696</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>N95</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkmtrFDEUhoMotl0Ff4EMiqjgrLnMZJJvLsVLoVDw9jXkcmZNO5OpSQbqvzfLrq6rghJIQs5zrnkRekDwkmAmXgaTl4Q3zS10TNqG14RLfrvcsehqTFp-hE5SusQY84bzu-iI4pZTwekxerWqxmlOUF2FyV5Nc64Gb6KO36p-ilUCGyGDq3RwVY46pBHGYg5QXccpgw_pHrrT6yHB_d25QJ_evP54-q4-v3h7dro6ry1vWK57KR1oShxnfWu05tiIjlJuHBBHoGlkZ7izummJMV1rnMCcWIoZZswIK9kCPd3GLYm_zpCyGn2yMAylmNKAEl1DBKaS_JPsGGslE6WsBXr0G3k5zTGUNhQnrOOc0U24x1torQdQPvRTGYTdhFQrykpOgSUr1PIvVFkORm-nAL0v7wcOzw8cCpPhJq_1nJI6-_D-_9mLz4fsi19YMycfIJUt-fWXnLYuB_izLW7jlFKEXl1HP5b_VwSrjbZU0ZbaaKugD3fTms0I7if4Q0wFeLIDdLJ66ItOrE97jmEiqWz37aRiCmuI-7H_kfQ7OAXfTw</recordid><startdate>20100701</startdate><enddate>20100701</enddate><creator>Tang, Tracy</creator><creator>Li, Li</creator><creator>Tang, Jerry</creator><creator>Li, Yun</creator><creator>Lin, Wei Yu</creator><creator>Martin, Flavius</creator><creator>Grant, Deanna</creator><creator>Solloway, Mark</creator><creator>Parker, Leon</creator><creator>Ye, Weilan</creator><creator>Forrest, William</creator><creator>Ghilardi, Nico</creator><creator>Oravecz, Tamas</creator><creator>Platt, Kenneth A</creator><creator>Rice, Dennis S</creator><creator>Hansen, Gwenn M</creator><creator>Abuin, Alejandro</creator><creator>Eberhart, Derek E</creator><creator>Godowski, Paul</creator><creator>Holt, Kathleen H</creator><creator>Peterson, Andrew</creator><creator>Zambrowicz, Brian P</creator><creator>de Sauvage, Frederic J</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</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>N95</scope><scope>XI7</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20100701</creationdate><title>A mouse knockout library for secreted and transmembrane proteins</title><author>Tang, Tracy ; Li, Li ; Tang, Jerry ; Li, Yun ; Lin, Wei Yu ; Martin, Flavius ; Grant, Deanna ; Solloway, Mark ; Parker, Leon ; Ye, Weilan ; Forrest, William ; Ghilardi, Nico ; Oravecz, Tamas ; Platt, Kenneth A ; Rice, Dennis S ; Hansen, Gwenn M ; Abuin, Alejandro ; Eberhart, Derek E ; Godowski, Paul ; Holt, Kathleen H ; Peterson, Andrew ; Zambrowicz, Brian P ; de Sauvage, Frederic J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c643t-f99dea21d63f5baa60b87226bde1d1e4497b6dca451bb75bd8061c203033b8c93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>631/1647/666/2262</topic><topic>631/61/17/1511</topic><topic>631/61/191</topic><topic>Agriculture</topic><topic>Animals</topic><topic>Bioinformatics</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering/Biotechnology</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>Cardiovascular system</topic><topic>Diverse techniques</topic><topic>Embryonic development</topic><topic>Embryonic growth stage</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genetically modified organisms</topic><topic>Health aspects</topic><topic>Immune system</topic><topic>Life Sciences</topic><topic>Membrane proteins</topic><topic>Membrane Proteins - genetics</topic><topic>Membranes</topic><topic>Methods</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Molecular and cellular biology</topic><topic>Properties</topic><topic>Proteins</topic><topic>resource</topic><topic>Rodents</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tang, Tracy</creatorcontrib><creatorcontrib>Li, Li</creatorcontrib><creatorcontrib>Tang, Jerry</creatorcontrib><creatorcontrib>Li, Yun</creatorcontrib><creatorcontrib>Lin, Wei Yu</creatorcontrib><creatorcontrib>Martin, Flavius</creatorcontrib><creatorcontrib>Grant, Deanna</creatorcontrib><creatorcontrib>Solloway, Mark</creatorcontrib><creatorcontrib>Parker, Leon</creatorcontrib><creatorcontrib>Ye, Weilan</creatorcontrib><creatorcontrib>Forrest, 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et al
. present the first large-scale, gene-specific library of knockout mice. They disrupt 472 genes encoding secreted or transmembrane proteins and report the results of a comprehensive phenotypic analysis.
Large collections of knockout organisms facilitate the elucidation of gene functions. Here we used retroviral insertion or homologous recombination to disrupt 472 genes encoding secreted and membrane proteins in mice, providing a resource for studying a large fraction of this important class of drug target. The knockout mice were subjected to a systematic phenotypic screen designed to uncover alterations in embryonic development, metabolism, the immune system, the nervous system and the cardiovascular system. The majority of knockout lines exhibited altered phenotypes in at least one of these therapeutic areas. To our knowledge, a comprehensive phenotypic assessment of a large number of mouse mutants generated by a gene-specific approach has not been described previously.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>20562862</pmid><doi>10.1038/nbt.1644</doi><tpages>7</tpages></addata></record> |
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subjects | 631/1647/666/2262 631/61/17/1511 631/61/191 Agriculture Animals Bioinformatics Biological and medical sciences Biomedical and Life Sciences Biomedical Engineering/Biotechnology Biomedicine Biotechnology Cardiovascular system Diverse techniques Embryonic development Embryonic growth stage Fundamental and applied biological sciences. Psychology Genetically modified organisms Health aspects Immune system Life Sciences Membrane proteins Membrane Proteins - genetics Membranes Methods Mice Mice, Knockout Molecular and cellular biology Properties Proteins resource Rodents |
title | A mouse knockout library for secreted and transmembrane proteins |
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