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Targeting and Germ-Line Transmission of a Null Mutation at the Metallothionein I and II Loci in Mouse
We report the generation of transgenic mice deficient in the metallothionein MT-I and MT-II genes. The mutations were introduced into embryonic stem cells by homologous recombination. Chimeric mice resulting from the targeted embryonic stem cells transmitted the disrupted alleles through their germ...
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| Published in: | Proceedings of the National Academy of Sciences - PNAS 1993-09, Vol.90 (17), p.8088-8092 |
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| container_end_page | 8092 |
| container_issue | 17 |
| container_start_page | 8088 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 90 |
| creator | Michalska, Anna E. K. H. Andy Choo |
| description | We report the generation of transgenic mice deficient in the metallothionein MT-I and MT-II genes. The mutations were introduced into embryonic stem cells by homologous recombination. Chimeric mice resulting from the targeted embryonic stem cells transmitted the disrupted alleles through their germ line. Homozygous animals were born alive and appeared phenotypically normal and fertile. Absence of MT proteins was confirmed by direct measurement in liver extracts. Challenging the mutant animals with moderate levels of CdSO4indicated their greater susceptibility to cadmium toxicity than wild-type animals. These mice should provide a useful model to allow detailed study of the physiological roles of MT-I and MT-II. |
| doi_str_mv | 10.1073/pnas.90.17.8088 |
| format | article |
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H. Andy Choo</creator><creatorcontrib>Michalska, Anna E. ; K. H. Andy Choo</creatorcontrib><description>We report the generation of transgenic mice deficient in the metallothionein MT-I and MT-II genes. The mutations were introduced into embryonic stem cells by homologous recombination. Chimeric mice resulting from the targeted embryonic stem cells transmitted the disrupted alleles through their germ line. Homozygous animals were born alive and appeared phenotypically normal and fertile. Absence of MT proteins was confirmed by direct measurement in liver extracts. Challenging the mutant animals with moderate levels of CdSO4indicated their greater susceptibility to cadmium toxicity than wild-type animals. These mice should provide a useful model to allow detailed study of the physiological roles of MT-I and MT-II.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.90.17.8088</identifier><identifier>PMID: 8367468</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences of the United States of America</publisher><subject>Alleles ; Animals ; Base Sequence ; Biological and medical sciences ; Biotechnology ; Blotting, Southern ; Cadmium ; Cell lines ; Chimera ; Crosses, Genetic ; DNA - genetics ; DNA - isolation & purification ; DNA probes ; Embryo, Mammalian ; Female ; Fetuses ; Fundamental and applied biological sciences. Psychology ; Genes ; Genetic Carrier Screening ; Genetic engineering ; Genetic loci ; Genetic mutation ; Genetic technics ; Homozygote ; Male ; Messenger RNA ; Metallothionein - deficiency ; Metallothionein - genetics ; Methods. Procedures. Technologies ; Mice ; Mice - genetics ; Mice, Inbred C57BL - genetics ; Molecular Sequence Data ; Mutation ; Oligodeoxyribonucleotides ; Polymerase chain reaction ; Polymerase Chain Reaction - methods ; Recombination, Genetic ; Restriction Mapping ; Rodents ; Stem Cells - metabolism ; Transgenic animals ; Transgenic animals and transgenic plants</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1993-09, Vol.90 (17), p.8088-8092</ispartof><rights>Copyright 1993 The National Academy of Sciences of the United States of America</rights><rights>1994 INIST-CNRS</rights><rights>Copyright National Academy of Sciences Sep 1, 1993</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5308-79bf76de7c46adee22a1815893b079f3976e30f2307c73e5a253c49965343ee53</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/90/17.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2362970$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2362970$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,53789,53791,58236,58469</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3755414$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8367468$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Michalska, Anna E.</creatorcontrib><creatorcontrib>K. H. Andy Choo</creatorcontrib><title>Targeting and Germ-Line Transmission of a Null Mutation at the Metallothionein I and II Loci in Mouse</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>We report the generation of transgenic mice deficient in the metallothionein MT-I and MT-II genes. The mutations were introduced into embryonic stem cells by homologous recombination. Chimeric mice resulting from the targeted embryonic stem cells transmitted the disrupted alleles through their germ line. Homozygous animals were born alive and appeared phenotypically normal and fertile. Absence of MT proteins was confirmed by direct measurement in liver extracts. Challenging the mutant animals with moderate levels of CdSO4indicated their greater susceptibility to cadmium toxicity than wild-type animals. These mice should provide a useful model to allow detailed study of the physiological roles of MT-I and MT-II.</description><subject>Alleles</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Blotting, Southern</subject><subject>Cadmium</subject><subject>Cell lines</subject><subject>Chimera</subject><subject>Crosses, Genetic</subject><subject>DNA - genetics</subject><subject>DNA - isolation & purification</subject><subject>DNA probes</subject><subject>Embryo, Mammalian</subject><subject>Female</subject><subject>Fetuses</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genes</subject><subject>Genetic Carrier Screening</subject><subject>Genetic engineering</subject><subject>Genetic loci</subject><subject>Genetic mutation</subject><subject>Genetic technics</subject><subject>Homozygote</subject><subject>Male</subject><subject>Messenger RNA</subject><subject>Metallothionein - deficiency</subject><subject>Metallothionein - genetics</subject><subject>Methods. Procedures. Technologies</subject><subject>Mice</subject><subject>Mice - genetics</subject><subject>Mice, Inbred C57BL - genetics</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Oligodeoxyribonucleotides</subject><subject>Polymerase chain reaction</subject><subject>Polymerase Chain Reaction - methods</subject><subject>Recombination, Genetic</subject><subject>Restriction Mapping</subject><subject>Rodents</subject><subject>Stem Cells - metabolism</subject><subject>Transgenic animals</subject><subject>Transgenic animals and transgenic plants</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><recordid>eNp9kUtvEzEUhUcIVNLCmg0gCyFYTerH-CWxQRWUSAlswtpynDvJRBM7tT0I_n09JESUBSvr3vPdl09VvSB4SrBk1wdv01SXQE4VVupRNSFYk1o0Gj-uJhhTWauGNk-ry5R2GGPNFb6oLhQTshFqUsHSxg3kzm-Q9Wt0C3FfzzsPaBmtT_supS54FFpk0deh79FiyDaPKZtR3gJaQLZ9H_K25KDzaPa7zWyG5sF1qCQWYUjwrHrS2j7B89N7VX3__Gl586Wef7ud3Xyc144zrGqpV60Ua5CuEXYNQKklinCl2QpL3TItBTDcUoalkwy4pZy5RmvBWcMAOLuqPhz7HobVHtYOfI62N4fY7W38ZYLtzEPFd1uzCT9MI6lmpfzdqTyGuwFSNuUDHPS99VDOMEQIobgQBXzzD7gLQ_TlNEMxoUpwjAt0fYRcDClFaM97EGxG88xontElkGY0r1S8-nv9M39yq-hvT7pNzvZtsch16YwxyXlDmoK9PmFj_z_qgznv_wuYtlid4Wcu5MsjuUs5xDNKmaBaYnYPPCHC9A</recordid><startdate>19930901</startdate><enddate>19930901</enddate><creator>Michalska, Anna E.</creator><creator>K. H. Andy Choo</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>National Academy of Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>19930901</creationdate><title>Targeting and Germ-Line Transmission of a Null Mutation at the Metallothionein I and II Loci in Mouse</title><author>Michalska, Anna E. ; K. H. Andy Choo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5308-79bf76de7c46adee22a1815893b079f3976e30f2307c73e5a253c49965343ee53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Alleles</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>Blotting, Southern</topic><topic>Cadmium</topic><topic>Cell lines</topic><topic>Chimera</topic><topic>Crosses, Genetic</topic><topic>DNA - genetics</topic><topic>DNA - isolation & purification</topic><topic>DNA probes</topic><topic>Embryo, Mammalian</topic><topic>Female</topic><topic>Fetuses</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genes</topic><topic>Genetic Carrier Screening</topic><topic>Genetic engineering</topic><topic>Genetic loci</topic><topic>Genetic mutation</topic><topic>Genetic technics</topic><topic>Homozygote</topic><topic>Male</topic><topic>Messenger RNA</topic><topic>Metallothionein - deficiency</topic><topic>Metallothionein - genetics</topic><topic>Methods. Procedures. Technologies</topic><topic>Mice</topic><topic>Mice - genetics</topic><topic>Mice, Inbred C57BL - genetics</topic><topic>Molecular Sequence Data</topic><topic>Mutation</topic><topic>Oligodeoxyribonucleotides</topic><topic>Polymerase chain reaction</topic><topic>Polymerase Chain Reaction - methods</topic><topic>Recombination, Genetic</topic><topic>Restriction Mapping</topic><topic>Rodents</topic><topic>Stem Cells - metabolism</topic><topic>Transgenic animals</topic><topic>Transgenic animals and transgenic plants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Michalska, Anna E.</creatorcontrib><creatorcontrib>K. H. Andy Choo</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>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Michalska, Anna E.</au><au>K. H. Andy Choo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeting and Germ-Line Transmission of a Null Mutation at the Metallothionein I and II Loci in Mouse</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1993-09-01</date><risdate>1993</risdate><volume>90</volume><issue>17</issue><spage>8088</spage><epage>8092</epage><pages>8088-8092</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>We report the generation of transgenic mice deficient in the metallothionein MT-I and MT-II genes. The mutations were introduced into embryonic stem cells by homologous recombination. Chimeric mice resulting from the targeted embryonic stem cells transmitted the disrupted alleles through their germ line. Homozygous animals were born alive and appeared phenotypically normal and fertile. Absence of MT proteins was confirmed by direct measurement in liver extracts. Challenging the mutant animals with moderate levels of CdSO4indicated their greater susceptibility to cadmium toxicity than wild-type animals. These mice should provide a useful model to allow detailed study of the physiological roles of MT-I and MT-II.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>8367468</pmid><doi>10.1073/pnas.90.17.8088</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1993-09, Vol.90 (17), p.8088-8092 |
| issn | 0027-8424 1091-6490 |
| language | eng |
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| source | PubMed Central (Open Access); JSTOR |
| subjects | Alleles Animals Base Sequence Biological and medical sciences Biotechnology Blotting, Southern Cadmium Cell lines Chimera Crosses, Genetic DNA - genetics DNA - isolation & purification DNA probes Embryo, Mammalian Female Fetuses Fundamental and applied biological sciences. Psychology Genes Genetic Carrier Screening Genetic engineering Genetic loci Genetic mutation Genetic technics Homozygote Male Messenger RNA Metallothionein - deficiency Metallothionein - genetics Methods. Procedures. Technologies Mice Mice - genetics Mice, Inbred C57BL - genetics Molecular Sequence Data Mutation Oligodeoxyribonucleotides Polymerase chain reaction Polymerase Chain Reaction - methods Recombination, Genetic Restriction Mapping Rodents Stem Cells - metabolism Transgenic animals Transgenic animals and transgenic plants |
| title | Targeting and Germ-Line Transmission of a Null Mutation at the Metallothionein I and II Loci in Mouse |
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