Functionally Complete Excision of Conditional Alleles in the Mouse Suprachiasmatic Nucleus by Vgat-ires-Cre
Mice with targeted gene disruption have provided important information about the molecular mechanisms of circadian clock function. A full understanding of the roles of circadian-relevant genes requires manipulation of their expression in a tissue-specific manner, ideally including manipulation with...
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Veröffentlicht in: | Journal of biological rhythms 2018-04, Vol.33 (2), p.179-191 |
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creator | Weaver, David R. van der Vinne, Vincent Giannaris, E. Lela Vajtay, Thomas J. Holloway, Kristopher L. Anaclet, Christelle |
description | Mice with targeted gene disruption have provided important information about the
molecular mechanisms of circadian clock function. A full understanding of the roles of
circadian-relevant genes requires manipulation of their expression in a tissue-specific
manner, ideally including manipulation with high efficiency within the suprachiasmatic
nuclei (SCN). To date, conditional manipulation of genes within the SCN has been
difficult. In a previously developed mouse line, Cre recombinase was inserted into the
vesicular GABA transporter (Vgat) locus. Since virtually all
SCN neurons are GABAergic, this Vgat-Cre line seemed likely
to have high efficiency at disrupting conditional alleles in SCN. To test this premise,
the efficacy of Vgat-Cre in excising conditional (fl, for
flanked by LoxP) alleles in the SCN was examined. Vgat-Cre-mediated excision of conditional alleles of Clock or Bmal1 led to loss of immunostaining for
products of the targeted genes in the SCN. Vgat-Cre+;
Clockfl/fl; Npas2m/m mice and Vgat-Cre+; Bmal1fl/fl mice became arrhythmic
immediately upon exposure to constant darkness, as expected based on the phenotype of mice
in which these genes are disrupted throughout the body. The phenotype of mice with other
combinations of Vgat-Cre+, conditional Clock, and mutant Npas2 alleles also
resembled the corresponding whole-body knockout mice. These data indicate that the Vgat-Cre line is useful for Cre-mediated recombination within the
SCN, making it useful for Cre-enabled technologies including gene disruption, gene
replacement, and opto- and chemogenetic manipulation of the SCN circadian clock. |
doi_str_mv | 10.1177/0748730418757006 |
format | Article |
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molecular mechanisms of circadian clock function. A full understanding of the roles of
circadian-relevant genes requires manipulation of their expression in a tissue-specific
manner, ideally including manipulation with high efficiency within the suprachiasmatic
nuclei (SCN). To date, conditional manipulation of genes within the SCN has been
difficult. In a previously developed mouse line, Cre recombinase was inserted into the
vesicular GABA transporter (Vgat) locus. Since virtually all
SCN neurons are GABAergic, this Vgat-Cre line seemed likely
to have high efficiency at disrupting conditional alleles in SCN. To test this premise,
the efficacy of Vgat-Cre in excising conditional (fl, for
flanked by LoxP) alleles in the SCN was examined. Vgat-Cre-mediated excision of conditional alleles of Clock or Bmal1 led to loss of immunostaining for
products of the targeted genes in the SCN. Vgat-Cre+;
Clockfl/fl; Npas2m/m mice and Vgat-Cre+; Bmal1fl/fl mice became arrhythmic
immediately upon exposure to constant darkness, as expected based on the phenotype of mice
in which these genes are disrupted throughout the body. The phenotype of mice with other
combinations of Vgat-Cre+, conditional Clock, and mutant Npas2 alleles also
resembled the corresponding whole-body knockout mice. These data indicate that the Vgat-Cre line is useful for Cre-mediated recombination within the
SCN, making it useful for Cre-enabled technologies including gene disruption, gene
replacement, and opto- and chemogenetic manipulation of the SCN circadian clock.</description><identifier>ISSN: 0748-7304</identifier><identifier>EISSN: 1552-4531</identifier><identifier>DOI: 10.1177/0748730418757006</identifier><identifier>PMID: 29671710</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Alleles ; Animals ; Biological clocks ; BMAL1 protein ; Circadian Clocks - genetics ; Circadian rhythm ; Circadian Rhythm - genetics ; Circadian rhythms ; CLOCK Proteins - genetics ; Cre recombinase ; Darkness ; Female ; Gene disruption ; Gene expression ; Genes ; Genetic engineering ; Integrases ; Male ; Mice ; Mice, Knockout ; Molecular chains ; Molecular modelling ; NPAS2 protein ; Phenotypes ; Recombination ; Suprachiasmatic Nucleus ; Vesicular Inhibitory Amino Acid Transport Proteins - genetics</subject><ispartof>Journal of biological rhythms, 2018-04, Vol.33 (2), p.179-191</ispartof><rights>2018 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c528t-64d39879a2d519e1aa39f95478bcde6d9f40c7f0ad868b5164596bddeec25ba53</citedby><cites>FETCH-LOGICAL-c528t-64d39879a2d519e1aa39f95478bcde6d9f40c7f0ad868b5164596bddeec25ba53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/0748730418757006$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/0748730418757006$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>230,314,780,784,885,21819,27924,27925,43621,43622</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29671710$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Weaver, David R.</creatorcontrib><creatorcontrib>van der Vinne, Vincent</creatorcontrib><creatorcontrib>Giannaris, E. Lela</creatorcontrib><creatorcontrib>Vajtay, Thomas J.</creatorcontrib><creatorcontrib>Holloway, Kristopher L.</creatorcontrib><creatorcontrib>Anaclet, Christelle</creatorcontrib><title>Functionally Complete Excision of Conditional Alleles in the Mouse Suprachiasmatic Nucleus by Vgat-ires-Cre</title><title>Journal of biological rhythms</title><addtitle>J Biol Rhythms</addtitle><description>Mice with targeted gene disruption have provided important information about the
molecular mechanisms of circadian clock function. A full understanding of the roles of
circadian-relevant genes requires manipulation of their expression in a tissue-specific
manner, ideally including manipulation with high efficiency within the suprachiasmatic
nuclei (SCN). To date, conditional manipulation of genes within the SCN has been
difficult. In a previously developed mouse line, Cre recombinase was inserted into the
vesicular GABA transporter (Vgat) locus. Since virtually all
SCN neurons are GABAergic, this Vgat-Cre line seemed likely
to have high efficiency at disrupting conditional alleles in SCN. To test this premise,
the efficacy of Vgat-Cre in excising conditional (fl, for
flanked by LoxP) alleles in the SCN was examined. Vgat-Cre-mediated excision of conditional alleles of Clock or Bmal1 led to loss of immunostaining for
products of the targeted genes in the SCN. Vgat-Cre+;
Clockfl/fl; Npas2m/m mice and Vgat-Cre+; Bmal1fl/fl mice became arrhythmic
immediately upon exposure to constant darkness, as expected based on the phenotype of mice
in which these genes are disrupted throughout the body. The phenotype of mice with other
combinations of Vgat-Cre+, conditional Clock, and mutant Npas2 alleles also
resembled the corresponding whole-body knockout mice. These data indicate that the Vgat-Cre line is useful for Cre-mediated recombination within the
SCN, making it useful for Cre-enabled technologies including gene disruption, gene
replacement, and opto- and chemogenetic manipulation of the SCN circadian clock.</description><subject>Alleles</subject><subject>Animals</subject><subject>Biological clocks</subject><subject>BMAL1 protein</subject><subject>Circadian Clocks - genetics</subject><subject>Circadian rhythm</subject><subject>Circadian Rhythm - genetics</subject><subject>Circadian rhythms</subject><subject>CLOCK Proteins - genetics</subject><subject>Cre recombinase</subject><subject>Darkness</subject><subject>Female</subject><subject>Gene disruption</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic engineering</subject><subject>Integrases</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Molecular chains</subject><subject>Molecular modelling</subject><subject>NPAS2 protein</subject><subject>Phenotypes</subject><subject>Recombination</subject><subject>Suprachiasmatic Nucleus</subject><subject>Vesicular Inhibitory Amino Acid Transport Proteins - genetics</subject><issn>0748-7304</issn><issn>1552-4531</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1v1DAQxS0EotvCnROyxIVLwE78eUGqVm1BKnDg42o59mTXxYkXO0Hsf49XWwpU4jTSvN-88fgh9IySV5RK-ZpIpmRHGFWSS0LEA7SinLcN4x19iFYHuTnoJ-i0lBtSCc26x-ik1UJSSckKfbtcJjeHNNkY93idxl2EGfDFTxdK7eI01ObkwxHB5zFChILDhOct4PdpKYA_Lbts3TbYMto5OPxhcRGWgvs9_rqxcxMylGad4Ql6NNhY4OltPUNfLi8-r9821x-v3q3PrxvHWzU3gvlOK6lt6znVQK3t9KA5k6p3HoTXAyNODsR6JVTPqWBci957ANfy3vLuDL05-u6WfgTvYJqzjWaXw2jz3iQbzL_KFLZmk34YwbSkXFSDl7cGOX1foMxmDMVBjHaCerFpSSu5UkzRir64h96kJdevOlCdEKLjSleKHCmXUykZhrvHUGIOSZr7SdaR538fcTfwO7oKNEeg2A382fpfw19lPKdp</recordid><startdate>201804</startdate><enddate>201804</enddate><creator>Weaver, David R.</creator><creator>van der Vinne, Vincent</creator><creator>Giannaris, E. Lela</creator><creator>Vajtay, Thomas J.</creator><creator>Holloway, Kristopher L.</creator><creator>Anaclet, Christelle</creator><general>SAGE Publications</general><general>SAGE PUBLICATIONS, INC</general><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>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201804</creationdate><title>Functionally Complete Excision of Conditional Alleles in the Mouse Suprachiasmatic Nucleus by Vgat-ires-Cre</title><author>Weaver, David R. ; van der Vinne, Vincent ; Giannaris, E. Lela ; Vajtay, Thomas J. ; Holloway, Kristopher L. ; Anaclet, Christelle</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c528t-64d39879a2d519e1aa39f95478bcde6d9f40c7f0ad868b5164596bddeec25ba53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Alleles</topic><topic>Animals</topic><topic>Biological clocks</topic><topic>BMAL1 protein</topic><topic>Circadian Clocks - genetics</topic><topic>Circadian rhythm</topic><topic>Circadian Rhythm - genetics</topic><topic>Circadian rhythms</topic><topic>CLOCK Proteins - genetics</topic><topic>Cre recombinase</topic><topic>Darkness</topic><topic>Female</topic><topic>Gene disruption</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic engineering</topic><topic>Integrases</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Molecular chains</topic><topic>Molecular modelling</topic><topic>NPAS2 protein</topic><topic>Phenotypes</topic><topic>Recombination</topic><topic>Suprachiasmatic Nucleus</topic><topic>Vesicular Inhibitory Amino Acid Transport Proteins - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Weaver, David R.</creatorcontrib><creatorcontrib>van der Vinne, Vincent</creatorcontrib><creatorcontrib>Giannaris, E. Lela</creatorcontrib><creatorcontrib>Vajtay, Thomas J.</creatorcontrib><creatorcontrib>Holloway, Kristopher L.</creatorcontrib><creatorcontrib>Anaclet, Christelle</creatorcontrib><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>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids 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>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of biological rhythms</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Weaver, David R.</au><au>van der Vinne, Vincent</au><au>Giannaris, E. Lela</au><au>Vajtay, Thomas J.</au><au>Holloway, Kristopher L.</au><au>Anaclet, Christelle</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functionally Complete Excision of Conditional Alleles in the Mouse Suprachiasmatic Nucleus by Vgat-ires-Cre</atitle><jtitle>Journal of biological rhythms</jtitle><addtitle>J Biol Rhythms</addtitle><date>2018-04</date><risdate>2018</risdate><volume>33</volume><issue>2</issue><spage>179</spage><epage>191</epage><pages>179-191</pages><issn>0748-7304</issn><eissn>1552-4531</eissn><abstract>Mice with targeted gene disruption have provided important information about the
molecular mechanisms of circadian clock function. A full understanding of the roles of
circadian-relevant genes requires manipulation of their expression in a tissue-specific
manner, ideally including manipulation with high efficiency within the suprachiasmatic
nuclei (SCN). To date, conditional manipulation of genes within the SCN has been
difficult. In a previously developed mouse line, Cre recombinase was inserted into the
vesicular GABA transporter (Vgat) locus. Since virtually all
SCN neurons are GABAergic, this Vgat-Cre line seemed likely
to have high efficiency at disrupting conditional alleles in SCN. To test this premise,
the efficacy of Vgat-Cre in excising conditional (fl, for
flanked by LoxP) alleles in the SCN was examined. Vgat-Cre-mediated excision of conditional alleles of Clock or Bmal1 led to loss of immunostaining for
products of the targeted genes in the SCN. Vgat-Cre+;
Clockfl/fl; Npas2m/m mice and Vgat-Cre+; Bmal1fl/fl mice became arrhythmic
immediately upon exposure to constant darkness, as expected based on the phenotype of mice
in which these genes are disrupted throughout the body. The phenotype of mice with other
combinations of Vgat-Cre+, conditional Clock, and mutant Npas2 alleles also
resembled the corresponding whole-body knockout mice. These data indicate that the Vgat-Cre line is useful for Cre-mediated recombination within the
SCN, making it useful for Cre-enabled technologies including gene disruption, gene
replacement, and opto- and chemogenetic manipulation of the SCN circadian clock.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>29671710</pmid><doi>10.1177/0748730418757006</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Alleles Animals Biological clocks BMAL1 protein Circadian Clocks - genetics Circadian rhythm Circadian Rhythm - genetics Circadian rhythms CLOCK Proteins - genetics Cre recombinase Darkness Female Gene disruption Gene expression Genes Genetic engineering Integrases Male Mice Mice, Knockout Molecular chains Molecular modelling NPAS2 protein Phenotypes Recombination Suprachiasmatic Nucleus Vesicular Inhibitory Amino Acid Transport Proteins - genetics |
title | Functionally Complete Excision of Conditional Alleles in the Mouse Suprachiasmatic Nucleus by Vgat-ires-Cre |
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