Rescue of Cardiac Defects in Id Knockout Embryos by Injection of Embryonic Stem Cells
We report that Id knockout mouse embryos display multiple cardiac defects, but mid-gestation lethality is rescued by the injection of 15 wild-type embryonic stem (ES) cells into mutant blastocysts. Myocardial markers altered in Id mutant cells are restored to normal throughout the chimeric myocardiu...
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Veröffentlicht in: | Science (American Association for the Advancement of Science) 2004-10, Vol.306 (5694), p.247-252 |
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creator | Fraidenraich, Diego Stillwell, Elizabeth Romero, Elizabeth Wilkes, David Manova, Katia Basson, Craig T. Benezra, Robert |
description | We report that Id knockout mouse embryos display multiple cardiac defects, but mid-gestation lethality is rescued by the injection of 15 wild-type embryonic stem (ES) cells into mutant blastocysts. Myocardial markers altered in Id mutant cells are restored to normal throughout the chimeric myocardium. Intraperitoneal injection of ES cells into female mice before conception also partially rescues the cardiac phenotype with no incorporation of ES cells. Insulin-like growth factor 1, a long-range secreted factor, in combination with WNT5a, a locally secreted factor, likely account for complete reversion of the cardiac phenotype. Thus, ES cells have the potential to reverse congenital defects through Id-dependent local and long-range effects in a mammalian embryo. |
doi_str_mv | 10.1126/science.1102612 |
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Myocardial markers altered in Id mutant cells are restored to normal throughout the chimeric myocardium. Intraperitoneal injection of ES cells into female mice before conception also partially rescues the cardiac phenotype with no incorporation of ES cells. Insulin-like growth factor 1, a long-range secreted factor, in combination with WNT5a, a locally secreted factor, likely account for complete reversion of the cardiac phenotype. Thus, ES cells have the potential to reverse congenital defects through Id-dependent local and long-range effects in a mammalian embryo.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1102612</identifier><identifier>PMID: 15472070</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Association for the Advancement of Science</publisher><subject>Animals ; Biological and medical sciences ; Birth defects ; Blastocyst ; Cardiology ; Cell Division ; Cell growth ; Cells, Cultured ; Classical genetics, quantitative genetics, hybrids ; DNA-Binding Proteins - genetics ; Embryo Loss ; Embryo, Mammalian - cytology ; Embryonic stem cells ; Embryos ; Endocardium ; Endothelial cells ; Epicardium ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Genetic aspects ; Genetics of eukaryotes. Biological and molecular evolution ; Heart ; Heart - embryology ; Heart Defects, Congenital - embryology ; Heart Defects, Congenital - therapy ; Individualized Instruction ; Inhibitor of Differentiation Protein 1 ; Inhibitor of Differentiation Protein 2 ; Insulin-Like Growth Factor I - genetics ; Insulin-Like Growth Factor I - physiology ; Maternal-Fetal Exchange ; Mice ; Mice, Knockout ; Myocardium ; Myocardium - cytology ; Myocardium - metabolism ; Myocytes, Cardiac - cytology ; Oligonucleotide Array Sequence Analysis ; Pathology ; Pericardium - embryology ; Pericardium - metabolism ; Physiological aspects ; Pollution ; Pregnancy ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins - physiology ; Pups ; Repressor Proteins - genetics ; Rodents ; Stem Cell Transplantation ; Stem cells ; Stem Cells - physiology ; Transcription Factors - genetics ; Vertebrata ; Wnt Proteins ; Wnt-5a Protein</subject><ispartof>Science (American Association for the Advancement of Science), 2004-10, Vol.306 (5694), p.247-252</ispartof><rights>Copyright 2004 American Association for the Advancement of Science</rights><rights>2005 INIST-CNRS</rights><rights>COPYRIGHT 2004 American Association for the Advancement of Science</rights><rights>COPYRIGHT 2004 American Association for the Advancement of Science</rights><rights>Copyright American Association for the Advancement of Science Oct 8, 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c743t-5aa30b0d5bddaabbe989fdce62ebd389fe637bb50f314c15fe244831af30e6ec3</citedby><cites>FETCH-LOGICAL-c743t-5aa30b0d5bddaabbe989fdce62ebd389fe637bb50f314c15fe244831af30e6ec3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3839204$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3839204$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,776,780,799,881,2871,2872,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16190173$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15472070$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fraidenraich, Diego</creatorcontrib><creatorcontrib>Stillwell, Elizabeth</creatorcontrib><creatorcontrib>Romero, Elizabeth</creatorcontrib><creatorcontrib>Wilkes, David</creatorcontrib><creatorcontrib>Manova, Katia</creatorcontrib><creatorcontrib>Basson, Craig T.</creatorcontrib><creatorcontrib>Benezra, Robert</creatorcontrib><title>Rescue of Cardiac Defects in Id Knockout Embryos by Injection of Embryonic Stem Cells</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>We report that Id knockout mouse embryos display multiple cardiac defects, but mid-gestation lethality is rescued by the injection of 15 wild-type embryonic stem (ES) cells into mutant blastocysts. Myocardial markers altered in Id mutant cells are restored to normal throughout the chimeric myocardium. Intraperitoneal injection of ES cells into female mice before conception also partially rescues the cardiac phenotype with no incorporation of ES cells. Insulin-like growth factor 1, a long-range secreted factor, in combination with WNT5a, a locally secreted factor, likely account for complete reversion of the cardiac phenotype. Thus, ES cells have the potential to reverse congenital defects through Id-dependent local and long-range effects in a mammalian embryo.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Birth defects</subject><subject>Blastocyst</subject><subject>Cardiology</subject><subject>Cell Division</subject><subject>Cell growth</subject><subject>Cells, Cultured</subject><subject>Classical genetics, quantitative genetics, hybrids</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Embryo Loss</subject><subject>Embryo, Mammalian - cytology</subject><subject>Embryonic stem cells</subject><subject>Embryos</subject><subject>Endocardium</subject><subject>Endothelial cells</subject><subject>Epicardium</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Genetic aspects</subject><subject>Genetics of eukaryotes. 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genetics</subject><subject>Proto-Oncogene Proteins - physiology</subject><subject>Pups</subject><subject>Repressor Proteins - genetics</subject><subject>Rodents</subject><subject>Stem Cell Transplantation</subject><subject>Stem cells</subject><subject>Stem Cells - physiology</subject><subject>Transcription Factors - genetics</subject><subject>Vertebrata</subject><subject>Wnt Proteins</subject><subject>Wnt-5a Protein</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqN091v0zAQAPAIgVgZPPOCUIQEiIds_oid5AVplFEqKioxxqvlOJfiLrFHnCD633NVo42iCqY8JLZ_d_JFd1H0lJITSpk8DcaCM4ALwiRl96IJJYVICkb4_WhCCJdJTjJxFD0KYU0InhX8YXRERZoxkpFJdPkFghkg9nU81V1ltYnfQw2mD7F18byKPzlvrvzQx-dt2W18iMtNPHdrFNa7bdhu31kTX_TQxlNomvA4elDrJsCT8X0cXX44_zr9mCyWs_n0bJGYLOV9IrTmpCSVKKtK67KEIi_qyoBkUFYcv0HyrCwFqTlNDRU1sDTNOdU1JyDB8OPo7S7v9VC2gJGu73Sjrjvb6m6jvLZq_8TZ72rlfyrKBSU0wwSvxwSd_zFA6FVrg8EStAM_BIXXTJlguUD56p9SyiJNGef_hTQnaZELifDFX3Dth87h_1IM71fkhKaIkh1a6QaUdbXHOswKHGA53kFtcfuMMi4ymfFt0pMDHp8KWmsOBrzZC0DTw69-pYcQ1Pzi893t8tvd7bvZnW0-W-zb5JA1vmlgBQrba7rc96c7bzofQgf1TXdQorYzpMYZUuMMYcTzP5vq1o9Dg-DlCHQwuqk77YwNt07SYttb6J7t3Dr0vrs55znH-Uz5b9yiKYo</recordid><startdate>20041008</startdate><enddate>20041008</enddate><creator>Fraidenraich, Diego</creator><creator>Stillwell, Elizabeth</creator><creator>Romero, Elizabeth</creator><creator>Wilkes, David</creator><creator>Manova, Katia</creator><creator>Basson, Craig T.</creator><creator>Benezra, Robert</creator><general>American Association for the Advancement of Science</general><general>The American Association for the Advancement of Science</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>8GL</scope><scope>IBG</scope><scope>IOV</scope><scope>ISN</scope><scope>0-V</scope><scope>3V.</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>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88B</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8BQ</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>ALSLI</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>CJNVE</scope><scope>D1I</scope><scope>DWQXO</scope><scope>F28</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>HCIFZ</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9-</scope><scope>K9.</scope><scope>KB.</scope><scope>KR7</scope><scope>L6V</scope><scope>L7M</scope><scope>LK8</scope><scope>L~C</scope><scope>L~D</scope><scope>M0K</scope><scope>M0P</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PCBAR</scope><scope>PDBOC</scope><scope>PQEDU</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>R05</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20041008</creationdate><title>Rescue of Cardiac Defects in Id Knockout Embryos by Injection of Embryonic Stem Cells</title><author>Fraidenraich, Diego ; Stillwell, Elizabeth ; Romero, Elizabeth ; Wilkes, David ; Manova, Katia ; Basson, Craig T. ; Benezra, Robert</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c743t-5aa30b0d5bddaabbe989fdce62ebd389fe637bb50f314c15fe244831af30e6ec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Birth defects</topic><topic>Blastocyst</topic><topic>Cardiology</topic><topic>Cell Division</topic><topic>Cell growth</topic><topic>Cells, Cultured</topic><topic>Classical genetics, quantitative genetics, hybrids</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Embryo Loss</topic><topic>Embryo, Mammalian - cytology</topic><topic>Embryonic stem cells</topic><topic>Embryos</topic><topic>Endocardium</topic><topic>Endothelial cells</topic><topic>Epicardium</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Genetic aspects</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Heart</topic><topic>Heart - embryology</topic><topic>Heart Defects, Congenital - embryology</topic><topic>Heart Defects, Congenital - therapy</topic><topic>Individualized Instruction</topic><topic>Inhibitor of Differentiation Protein 1</topic><topic>Inhibitor of Differentiation Protein 2</topic><topic>Insulin-Like Growth Factor I - genetics</topic><topic>Insulin-Like Growth Factor I - physiology</topic><topic>Maternal-Fetal Exchange</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Myocardium</topic><topic>Myocardium - cytology</topic><topic>Myocardium - metabolism</topic><topic>Myocytes, Cardiac - cytology</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Pathology</topic><topic>Pericardium - embryology</topic><topic>Pericardium - metabolism</topic><topic>Physiological aspects</topic><topic>Pollution</topic><topic>Pregnancy</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogene 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Knockout Embryos by Injection of Embryonic Stem Cells</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2004-10-08</date><risdate>2004</risdate><volume>306</volume><issue>5694</issue><spage>247</spage><epage>252</epage><pages>247-252</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>We report that Id knockout mouse embryos display multiple cardiac defects, but mid-gestation lethality is rescued by the injection of 15 wild-type embryonic stem (ES) cells into mutant blastocysts. Myocardial markers altered in Id mutant cells are restored to normal throughout the chimeric myocardium. Intraperitoneal injection of ES cells into female mice before conception also partially rescues the cardiac phenotype with no incorporation of ES cells. Insulin-like growth factor 1, a long-range secreted factor, in combination with WNT5a, a locally secreted factor, likely account for complete reversion of the cardiac phenotype. Thus, ES cells have the potential to reverse congenital defects through Id-dependent local and long-range effects in a mammalian embryo.</abstract><cop>Washington, DC</cop><pub>American Association for the Advancement of Science</pub><pmid>15472070</pmid><doi>10.1126/science.1102612</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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source | American Association for the Advancement of Science; Jstor Complete Legacy; MEDLINE |
subjects | Animals Biological and medical sciences Birth defects Blastocyst Cardiology Cell Division Cell growth Cells, Cultured Classical genetics, quantitative genetics, hybrids DNA-Binding Proteins - genetics Embryo Loss Embryo, Mammalian - cytology Embryonic stem cells Embryos Endocardium Endothelial cells Epicardium Female Fundamental and applied biological sciences. Psychology Gene Expression Profiling Gene Expression Regulation, Developmental Genetic aspects Genetics of eukaryotes. Biological and molecular evolution Heart Heart - embryology Heart Defects, Congenital - embryology Heart Defects, Congenital - therapy Individualized Instruction Inhibitor of Differentiation Protein 1 Inhibitor of Differentiation Protein 2 Insulin-Like Growth Factor I - genetics Insulin-Like Growth Factor I - physiology Maternal-Fetal Exchange Mice Mice, Knockout Myocardium Myocardium - cytology Myocardium - metabolism Myocytes, Cardiac - cytology Oligonucleotide Array Sequence Analysis Pathology Pericardium - embryology Pericardium - metabolism Physiological aspects Pollution Pregnancy Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - physiology Pups Repressor Proteins - genetics Rodents Stem Cell Transplantation Stem cells Stem Cells - physiology Transcription Factors - genetics Vertebrata Wnt Proteins Wnt-5a Protein |
title | Rescue of Cardiac Defects in Id Knockout Embryos by Injection of Embryonic Stem Cells |
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