Knockout Rats via Embryo Microinjection of Zinc-Finger Nucleases
The toolbox of rat genetics currently lacks the ability to introduce site-directed, heritable mutations into the genome to create knockout animals. By using engineered zinc-finger nucleases (ZFNs) designed to target an integrated reporter and two endogenous rat genes, Immunoglobulin M (IgM) and Rab3...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2009-07, Vol.325 (5939), p.433-433 |
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| creator | Geurts, Aron M Cost, Gregory J Freyvert, Yevgeniy Zeitler, Bryan Miller, Jeffrey C Choi, Vivian M Jenkins, Shirin S Wood, Adam Cui, Xiaoxia Meng, Xiangdong Vincent, Anna Lam, Stephen Michalkiewicz, Mieczyslaw Schilling, Rebecca Foeckler, Jamie Kalloway, Shawn Weiler, Hartmut Ménoret, Séverine Anegon, Ignacio Davis, Gregory D Zhang, Lei Rebar, Edward J Gregory, Philip D Urnov, Fyodor D Jacob, Howard J Buelow, Roland |
| description | The toolbox of rat genetics currently lacks the ability to introduce site-directed, heritable mutations into the genome to create knockout animals. By using engineered zinc-finger nucleases (ZFNs) designed to target an integrated reporter and two endogenous rat genes, Immunoglobulin M (IgM) and Rab38, we demonstrate that a single injection of DNA or messenger RNA encoding ZFNs into the one-cell rat embryo leads to a high frequency of animals carrying 25 to 100% disruption at the target locus. These mutations are faithfully and efficiently transmitted through the germline. Our data demonstrate the feasibility of targeted gene disruption in multiple rat strains within 4 months time, paving the way to a humanized monoclonal antibody platform and additional human disease models. |
| doi_str_mv | 10.1126/science.1172447 |
| format | Article |
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By using engineered zinc-finger nucleases (ZFNs) designed to target an integrated reporter and two endogenous rat genes, Immunoglobulin M (IgM) and Rab38, we demonstrate that a single injection of DNA or messenger RNA encoding ZFNs into the one-cell rat embryo leads to a high frequency of animals carrying 25 to 100% disruption at the target locus. These mutations are faithfully and efficiently transmitted through the germline. Our data demonstrate the feasibility of targeted gene disruption in multiple rat strains within 4 months time, paving the way to a humanized monoclonal antibody platform and additional human disease models.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1172447</identifier><identifier>PMID: 19628861</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Association for the Advancement of Science</publisher><subject>Animals ; Base Sequence ; Biological and medical sciences ; Brevia ; Classical genetics, quantitative genetics, hybrids ; Deoxyribonucleic acid ; Disease models ; DNA ; Embryo, Mammalian ; Embryos ; Endodeoxyribonucleases - genetics ; Endodeoxyribonucleases - metabolism ; Feasibility Studies ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Knockout Techniques ; Genetic mutation ; Genetic research ; Genetics of eukaryotes. Biological and molecular evolution ; Green Fluorescent Proteins ; Immunoglobulin M - genetics ; Inbreeding ; Male ; Messenger RNA ; Microinjections ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Mutation ; rab GTP-Binding Proteins - genetics ; Rats ; Ribonucleic acid ; RNA ; RNA, Messenger ; Rodents ; Vertebrata ; Zinc Fingers - genetics</subject><ispartof>Science (American Association for the Advancement of Science), 2009-07, Vol.325 (5939), p.433-433</ispartof><rights>Copyright 2009 American Association for the Advancement of Science</rights><rights>2009 INIST-CNRS</rights><rights>Copyright © 2009, American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c628t-393b6dd74f6c4796974a972ce485af7591b856a2c245fcc5c0822134eaa05aee3</citedby><cites>FETCH-LOGICAL-c628t-393b6dd74f6c4796974a972ce485af7591b856a2c245fcc5c0822134eaa05aee3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/20536698$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/20536698$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,2871,2872,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21790532$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19628861$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Geurts, Aron M</creatorcontrib><creatorcontrib>Cost, Gregory J</creatorcontrib><creatorcontrib>Freyvert, Yevgeniy</creatorcontrib><creatorcontrib>Zeitler, Bryan</creatorcontrib><creatorcontrib>Miller, Jeffrey C</creatorcontrib><creatorcontrib>Choi, Vivian M</creatorcontrib><creatorcontrib>Jenkins, Shirin S</creatorcontrib><creatorcontrib>Wood, Adam</creatorcontrib><creatorcontrib>Cui, Xiaoxia</creatorcontrib><creatorcontrib>Meng, Xiangdong</creatorcontrib><creatorcontrib>Vincent, Anna</creatorcontrib><creatorcontrib>Lam, Stephen</creatorcontrib><creatorcontrib>Michalkiewicz, Mieczyslaw</creatorcontrib><creatorcontrib>Schilling, Rebecca</creatorcontrib><creatorcontrib>Foeckler, Jamie</creatorcontrib><creatorcontrib>Kalloway, Shawn</creatorcontrib><creatorcontrib>Weiler, Hartmut</creatorcontrib><creatorcontrib>Ménoret, Séverine</creatorcontrib><creatorcontrib>Anegon, Ignacio</creatorcontrib><creatorcontrib>Davis, Gregory D</creatorcontrib><creatorcontrib>Zhang, Lei</creatorcontrib><creatorcontrib>Rebar, Edward J</creatorcontrib><creatorcontrib>Gregory, Philip D</creatorcontrib><creatorcontrib>Urnov, Fyodor D</creatorcontrib><creatorcontrib>Jacob, Howard J</creatorcontrib><creatorcontrib>Buelow, Roland</creatorcontrib><title>Knockout Rats via Embryo Microinjection of Zinc-Finger Nucleases</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>The toolbox of rat genetics currently lacks the ability to introduce site-directed, heritable mutations into the genome to create knockout animals. By using engineered zinc-finger nucleases (ZFNs) designed to target an integrated reporter and two endogenous rat genes, Immunoglobulin M (IgM) and Rab38, we demonstrate that a single injection of DNA or messenger RNA encoding ZFNs into the one-cell rat embryo leads to a high frequency of animals carrying 25 to 100% disruption at the target locus. These mutations are faithfully and efficiently transmitted through the germline. Our data demonstrate the feasibility of targeted gene disruption in multiple rat strains within 4 months time, paving the way to a humanized monoclonal antibody platform and additional human disease models.</description><subject>Animals</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Brevia</subject><subject>Classical genetics, quantitative genetics, hybrids</subject><subject>Deoxyribonucleic acid</subject><subject>Disease models</subject><subject>DNA</subject><subject>Embryo, Mammalian</subject><subject>Embryos</subject><subject>Endodeoxyribonucleases - genetics</subject><subject>Endodeoxyribonucleases - metabolism</subject><subject>Feasibility Studies</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Knockout Techniques</subject><subject>Genetic mutation</subject><subject>Genetic research</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Green Fluorescent Proteins</subject><subject>Immunoglobulin M - genetics</subject><subject>Inbreeding</subject><subject>Male</subject><subject>Messenger RNA</subject><subject>Microinjections</subject><subject>Molecular Sequence Data</subject><subject>Mutagenesis, Site-Directed</subject><subject>Mutation</subject><subject>rab GTP-Binding Proteins - genetics</subject><subject>Rats</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Messenger</subject><subject>Rodents</subject><subject>Vertebrata</subject><subject>Zinc Fingers - genetics</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1rFTEUhoMo7e3H2pU6CO1u2nPynZ1SWitWBbUbN0NubqbkOjepyUyh_74pd7DgpqsQnidvkvMS8hrhBJHK0-KCj87XjaKcqxdkgWBEayiwl2QBwGSrQYldslfKGqAyw3bILhpJtZa4IB--xOT-pGlsftixNHfBNuebZb5Pzdfgcgpx7d0YUmxS3_wO0bUXId743Hyb3OBt8eWAvOrtUPzhvO6T64vzX2eX7dX3T5_PPl61rl41tsywpVytFO-l48pIo7g1ijrPtbC9EgaXWkhLHeWid0440JQi495aENZ7tk-Ot7m3Of2dfBm7TSjOD4ONPk2lY4KiBqaeFSmiplzj8yJIg3XKVXz_n7hOU471tzWMSQBORZVOt1KdWinZ991tDhub7zuE7rGrbu6qm7uqJ97OsdNy41dP_lxOFY5mwRZnhz7b6EL551FUBgR7fN-brbcuY8pPvEIpja783Zb3NnX2JteM658UkAFKoTmT7AGwx64S</recordid><startdate>20090724</startdate><enddate>20090724</enddate><creator>Geurts, Aron M</creator><creator>Cost, Gregory J</creator><creator>Freyvert, Yevgeniy</creator><creator>Zeitler, Bryan</creator><creator>Miller, Jeffrey C</creator><creator>Choi, Vivian M</creator><creator>Jenkins, Shirin S</creator><creator>Wood, Adam</creator><creator>Cui, Xiaoxia</creator><creator>Meng, Xiangdong</creator><creator>Vincent, Anna</creator><creator>Lam, Stephen</creator><creator>Michalkiewicz, Mieczyslaw</creator><creator>Schilling, Rebecca</creator><creator>Foeckler, Jamie</creator><creator>Kalloway, Shawn</creator><creator>Weiler, Hartmut</creator><creator>Ménoret, Séverine</creator><creator>Anegon, Ignacio</creator><creator>Davis, Gregory D</creator><creator>Zhang, Lei</creator><creator>Rebar, Edward J</creator><creator>Gregory, Philip D</creator><creator>Urnov, Fyodor D</creator><creator>Jacob, Howard J</creator><creator>Buelow, Roland</creator><general>American Association for the Advancement of Science</general><general>The American Association for the Advancement of Science</general><scope>FBQ</scope><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>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7QO</scope></search><sort><creationdate>20090724</creationdate><title>Knockout Rats via Embryo Microinjection of Zinc-Finger Nucleases</title><author>Geurts, Aron M ; Cost, Gregory J ; Freyvert, Yevgeniy ; Zeitler, Bryan ; Miller, Jeffrey C ; Choi, Vivian M ; Jenkins, Shirin S ; Wood, Adam ; Cui, Xiaoxia ; Meng, Xiangdong ; Vincent, Anna ; Lam, Stephen ; Michalkiewicz, Mieczyslaw ; Schilling, Rebecca ; Foeckler, Jamie ; Kalloway, Shawn ; Weiler, Hartmut ; Ménoret, Séverine ; Anegon, Ignacio ; Davis, Gregory D ; Zhang, Lei ; Rebar, Edward J ; Gregory, Philip D ; Urnov, Fyodor D ; Jacob, Howard J ; Buelow, Roland</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c628t-393b6dd74f6c4796974a972ce485af7591b856a2c245fcc5c0822134eaa05aee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Brevia</topic><topic>Classical genetics, quantitative genetics, hybrids</topic><topic>Deoxyribonucleic acid</topic><topic>Disease models</topic><topic>DNA</topic><topic>Embryo, Mammalian</topic><topic>Embryos</topic><topic>Endodeoxyribonucleases - genetics</topic><topic>Endodeoxyribonucleases - metabolism</topic><topic>Feasibility Studies</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Knockout Techniques</topic><topic>Genetic mutation</topic><topic>Genetic research</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Green Fluorescent Proteins</topic><topic>Immunoglobulin M - genetics</topic><topic>Inbreeding</topic><topic>Male</topic><topic>Messenger RNA</topic><topic>Microinjections</topic><topic>Molecular Sequence Data</topic><topic>Mutagenesis, Site-Directed</topic><topic>Mutation</topic><topic>rab GTP-Binding Proteins - genetics</topic><topic>Rats</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Messenger</topic><topic>Rodents</topic><topic>Vertebrata</topic><topic>Zinc Fingers - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Geurts, Aron M</creatorcontrib><creatorcontrib>Cost, Gregory J</creatorcontrib><creatorcontrib>Freyvert, Yevgeniy</creatorcontrib><creatorcontrib>Zeitler, Bryan</creatorcontrib><creatorcontrib>Miller, Jeffrey C</creatorcontrib><creatorcontrib>Choi, Vivian M</creatorcontrib><creatorcontrib>Jenkins, Shirin S</creatorcontrib><creatorcontrib>Wood, 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By using engineered zinc-finger nucleases (ZFNs) designed to target an integrated reporter and two endogenous rat genes, Immunoglobulin M (IgM) and Rab38, we demonstrate that a single injection of DNA or messenger RNA encoding ZFNs into the one-cell rat embryo leads to a high frequency of animals carrying 25 to 100% disruption at the target locus. These mutations are faithfully and efficiently transmitted through the germline. Our data demonstrate the feasibility of targeted gene disruption in multiple rat strains within 4 months time, paving the way to a humanized monoclonal antibody platform and additional human disease models.</abstract><cop>Washington, DC</cop><pub>American Association for the Advancement of Science</pub><pmid>19628861</pmid><doi>10.1126/science.1172447</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 2009-07, Vol.325 (5939), p.433-433 |
| issn | 0036-8075 1095-9203 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_35218037 |
| source | Jstor Complete Legacy; MEDLINE; Science Magazine |
| subjects | Animals Base Sequence Biological and medical sciences Brevia Classical genetics, quantitative genetics, hybrids Deoxyribonucleic acid Disease models DNA Embryo, Mammalian Embryos Endodeoxyribonucleases - genetics Endodeoxyribonucleases - metabolism Feasibility Studies Female Fundamental and applied biological sciences. Psychology Gene Knockout Techniques Genetic mutation Genetic research Genetics of eukaryotes. Biological and molecular evolution Green Fluorescent Proteins Immunoglobulin M - genetics Inbreeding Male Messenger RNA Microinjections Molecular Sequence Data Mutagenesis, Site-Directed Mutation rab GTP-Binding Proteins - genetics Rats Ribonucleic acid RNA RNA, Messenger Rodents Vertebrata Zinc Fingers - genetics |
| title | Knockout Rats via Embryo Microinjection of Zinc-Finger Nucleases |
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