A Transgenic Prox1-Cre-tdTomato Reporter Mouse for Lymphatic Vessel Research
Identifieur interne : 007225 ( Ncbi/Merge ); précédent : 007224; suivant : 007226A Transgenic Prox1-Cre-tdTomato Reporter Mouse for Lymphatic Vessel Research
Auteurs : Roberta Bianchi [Suisse] ; Alvaro Teijeira [Suisse] ; Steven T. Proulx [Suisse] ; Ailsa J. Christiansen [Suisse] ; Catharina D. Seidel [Suisse] ; Thomas Rülicke [Autriche] ; Taija M Kinen [Suède] ; René H Gerling [Allemagne] ; Cornelia Halin [Suisse] ; Michael Detmar [Suisse]Source :
- PLoS ONE [ 1932-6203 ] ; 2015.
Abstract
The lymphatic vascular system plays an active role in immune cell trafficking, inflammation and cancer spread. In order to provide an
Url:
DOI: 10.1371/journal.pone.0122976
PubMed: 25849579
PubMed Central: 4388455
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PMC:4388455Le document en format XML
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Vascular Cell Biology, Max-Planck Institute for Molecular Biomedicine, Münster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Mammalian Cell Signaling Laboratory, Department of Vascular Cell Biology, Max-Planck Institute for Molecular Biomedicine, Münster</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Münster</region><settlement type="city">Münster</settlement></placeName></affiliation></author><author><name sortKey="Halin, Cornelia" sort="Halin, Cornelia" uniqKey="Halin C" first="Cornelia" last="Halin">Cornelia Halin</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich</wicri:regionArea><wicri:noRegion>Zurich</wicri:noRegion></affiliation></author><author><name sortKey="Detmar, Michael" sort="Detmar, Michael" uniqKey="Detmar M" first="Michael" last="Detmar">Michael Detmar</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich</wicri:regionArea><wicri:noRegion>Zurich</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25849579</idno><idno type="pmc">4388455</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388455</idno><idno type="RBID">PMC:4388455</idno><idno type="doi">10.1371/journal.pone.0122976</idno><date when="2015">2015</date><idno 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xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich</wicri:regionArea><wicri:noRegion>Zurich</wicri:noRegion></affiliation></author><author><name sortKey="Teijeira, Alvaro" sort="Teijeira, Alvaro" uniqKey="Teijeira A" first="Alvaro" last="Teijeira">Alvaro Teijeira</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich</wicri:regionArea><wicri:noRegion>Zurich</wicri:noRegion></affiliation></author><author><name sortKey="Proulx, Steven T" sort="Proulx, Steven T" uniqKey="Proulx S" first="Steven T." last="Proulx">Steven T. Proulx</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich</wicri:regionArea><wicri:noRegion>Zurich</wicri:noRegion></affiliation></author><author><name sortKey="Christiansen, Ailsa J" sort="Christiansen, Ailsa J" uniqKey="Christiansen A" first="Ailsa J." last="Christiansen">Ailsa J. Christiansen</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich</wicri:regionArea><wicri:noRegion>Zurich</wicri:noRegion></affiliation></author><author><name sortKey="Seidel, Catharina D" sort="Seidel, Catharina D" uniqKey="Seidel C" first="Catharina D." last="Seidel">Catharina D. Seidel</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich</wicri:regionArea><wicri:noRegion>Zurich</wicri:noRegion></affiliation></author><author><name sortKey="Rulicke, Thomas" sort="Rulicke, Thomas" uniqKey="Rulicke T" first="Thomas" last="Rülicke">Thomas Rülicke</name><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Institute of Laboratory Animal Sciences, University of Veterinary Medicine, Vienna, Austria</addr-line></nlm:aff><country xml:lang="fr">Autriche</country><wicri:regionArea>Institute of Laboratory Animal Sciences, University of Veterinary Medicine, Vienna</wicri:regionArea><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author><author><name sortKey="M Kinen, Taija" sort="M Kinen, Taija" uniqKey="M Kinen T" first="Taija" last="M Kinen">Taija M Kinen</name><affiliation wicri:level="4"><nlm:aff id="aff003"><addr-line>Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden</addr-line></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala</wicri:regionArea><orgName type="university">Université d'Uppsala</orgName><placeName><settlement type="city">Uppsala</settlement><region nuts="1">Svealand</region><region nuts="1">East Middle Sweden</region></placeName></affiliation></author><author><name sortKey="H Gerling, Rene" sort="H Gerling, Rene" uniqKey="H Gerling R" first="René" last="H Gerling">René H Gerling</name><affiliation wicri:level="3"><nlm:aff id="aff004"><addr-line>Mammalian Cell Signaling Laboratory, Department of Vascular Cell Biology, Max-Planck Institute for Molecular Biomedicine, Münster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Mammalian Cell Signaling Laboratory, Department of Vascular Cell Biology, Max-Planck Institute for Molecular Biomedicine, Münster</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Münster</region><settlement type="city">Münster</settlement></placeName></affiliation></author><author><name sortKey="Halin, Cornelia" sort="Halin, Cornelia" uniqKey="Halin C" first="Cornelia" last="Halin">Cornelia Halin</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich</wicri:regionArea><wicri:noRegion>Zurich</wicri:noRegion></affiliation></author><author><name sortKey="Detmar, Michael" sort="Detmar, Michael" uniqKey="Detmar M" first="Michael" last="Detmar">Michael Detmar</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich</wicri:regionArea><wicri:noRegion>Zurich</wicri:noRegion></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The lymphatic vascular system plays an active role in immune cell trafficking, inflammation and cancer spread. In order to provide an <italic>in vivo</italic> tool to improve our understanding of lymphatic vessel function in physiological and pathological conditions, we generated and characterized a tdTomato reporter mouse and crossed it with a mouse line expressing Cre recombinase under the control of the lymphatic specific promoter Prox1 in an inducible fashion. We found that the tdTomato fluorescent signal recapitulates the expression pattern of Prox1 in lymphatic vessels and other known Prox1-expressing organs. Importantly, tdTomato co-localized with the lymphatic markers Prox1, LYVE-1 and podoplanin as assessed by whole-mount immunofluorescence and FACS analysis. The tdTomato reporter was brighter than a previously established red fluorescent reporter line. We confirmed the applicability of this animal model to intravital microscopy of dendritic cell migration into and within lymphatic vessels, and to fluorescence-activated single cell analysis of lymphatic endothelial cells. Additionally, we were able to describe the early morphological changes of the lymphatic vasculature upon induction of skin inflammation. The Prox1-Cre-tdTomato reporter mouse thus shows great potential for lymphatic research.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Jurisic, G" uniqKey="Jurisic G">G Jurisic</name></author><author><name sortKey="Detmar, M" uniqKey="Detmar M">M Detmar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alitalo, K" uniqKey="Alitalo K">K Alitalo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alitalo, A" uniqKey="Alitalo A">A Alitalo</name></author><author><name sortKey="Detmar, M" uniqKey="Detmar M">M Detmar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dieterich, Lc" uniqKey="Dieterich L">LC Dieterich</name></author><author><name sortKey="Seidel, Cd" uniqKey="Seidel C">CD Seidel</name></author><author><name sortKey="Detmar, M" uniqKey="Detmar M">M 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, CA USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25849579</article-id><article-id pub-id-type="pmc">4388455</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0122976</article-id><article-id pub-id-type="publisher-id">PONE-D-14-36292</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>A Transgenic Prox1-Cre-tdTomato Reporter Mouse for Lymphatic Vessel Research</article-title><alt-title alt-title-type="running-head">A tdTomato Reporter Mouse for Lymphatic Research</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Bianchi</surname><given-names>Roberta</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Teijeira</surname><given-names>Alvaro</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Proulx</surname><given-names>Steven T.</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Christiansen</surname><given-names>Ailsa J.</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Seidel</surname><given-names>Catharina D.</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rülicke</surname><given-names>Thomas</given-names></name><xref ref-type="aff" rid="aff002"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mäkinen</surname><given-names>Taija</given-names></name><xref ref-type="aff" rid="aff003"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hägerling</surname><given-names>René</given-names></name><xref ref-type="aff" rid="aff004"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Halin</surname><given-names>Cornelia</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Detmar</surname><given-names>Michael</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref rid="cor001" ref-type="corresp">*</xref></contrib></contrib-group><aff id="aff001"><label>1</label><addr-line>Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland</addr-line></aff><aff id="aff002"><label>2</label><addr-line>Institute of Laboratory Animal Sciences, University of Veterinary Medicine, Vienna, Austria</addr-line></aff><aff id="aff003"><label>3</label><addr-line>Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden</addr-line></aff><aff id="aff004"><label>4</label><addr-line>Mammalian Cell Signaling Laboratory, Department of Vascular Cell Biology, Max-Planck Institute for Molecular Biomedicine, Münster, Germany</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Hogan</surname><given-names>Ben</given-names></name><role>Academic Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>University of Queensland, AUSTRALIA</addr-line></aff><author-notes><fn fn-type="conflict" id="coi001"><p><bold>Competing Interests: </bold>The authors have declared that no competing interests exist.</p></fn><fn fn-type="con" id="contrib001"><p>Conceived and designed the experiments: RB MD. Performed the experiments: RB AT STP AJC CDS. Analyzed the data: RB AT STP AJC CDS CH MD. Contributed reagents/materials/analysis tools: CH TR TM RH. Wrote the paper: RB MD.</p></fn><corresp id="cor001">* E-mail: <email>michael.detmar@pharma.ethz.ch</email></corresp></author-notes><pub-date pub-type="epub"><day>7</day><month>4</month><year>2015</year></pub-date><pub-date pub-type="collection"><year>2015</year></pub-date><volume>10</volume><issue>4</issue><elocation-id>e0122976</elocation-id><history><date date-type="received"><day>12</day><month>8</month><year>2014</year></date><date date-type="accepted"><day>26</day><month>2</month><year>2015</year></date></history><permissions><copyright-year>2015</copyright-year><copyright-holder>Bianchi et al</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited</license-p></license></permissions><self-uri content-type="pdf" xlink:type="simple" xlink:href="pone.0122976.pdf"></self-uri><abstract><p>The lymphatic vascular system plays an active role in immune cell trafficking, inflammation and cancer spread. In order to provide an <italic>in vivo</italic> tool to improve our understanding of lymphatic vessel function in physiological and pathological conditions, we generated and characterized a tdTomato reporter mouse and crossed it with a mouse line expressing Cre recombinase under the control of the lymphatic specific promoter Prox1 in an inducible fashion. We found that the tdTomato fluorescent signal recapitulates the expression pattern of Prox1 in lymphatic vessels and other known Prox1-expressing organs. Importantly, tdTomato co-localized with the lymphatic markers Prox1, LYVE-1 and podoplanin as assessed by whole-mount immunofluorescence and FACS analysis. The tdTomato reporter was brighter than a previously established red fluorescent reporter line. We confirmed the applicability of this animal model to intravital microscopy of dendritic cell migration into and within lymphatic vessels, and to fluorescence-activated single cell analysis of lymphatic endothelial cells. Additionally, we were able to describe the early morphological changes of the lymphatic vasculature upon induction of skin inflammation. The Prox1-Cre-tdTomato reporter mouse thus shows great potential for lymphatic research.</p></abstract><funding-group><funding-statement>This work was supported by Swiss National Science Foundation grant 31003A-130627, Advanced European Research Council Grant LYVICAM, the Leducq Foundation Transatlantic Network of Excellence grant Lymph Vessels in Obesity and Cardiovascular Disease, Oncosuisse and Krebsliga Zurich (to M.D.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><fig-count count="8"></fig-count><table-count count="0"></table-count><page-count count="18"></page-count></counts><custom-meta-group><custom-meta id="data-availability"><meta-name>Data Availability</meta-name><meta-value>All relevant data are within the paper and its Supporting Information files.</meta-value></custom-meta></custom-meta-group></article-meta><notes><title>Data Availability</title><p>All relevant data are within the paper and its Supporting Information files.</p></notes></front></pmc><affiliations><list><country><li>Allemagne</li><li>Autriche</li><li>Suisse</li><li>Suède</li></country><region><li>District de Münster</li><li>East Middle Sweden</li><li>Rhénanie-du-Nord-Westphalie</li><li>Svealand</li><li>Vienne (Autriche)</li></region><settlement><li>Münster</li><li>Uppsala</li><li>Vienne (Autriche)</li></settlement><orgName><li>Université d'Uppsala</li></orgName></list><tree><country name="Suisse"><noRegion><name sortKey="Bianchi, Roberta" sort="Bianchi, Roberta" uniqKey="Bianchi R" first="Roberta" last="Bianchi">Roberta Bianchi</name></noRegion><name sortKey="Christiansen, Ailsa J" sort="Christiansen, Ailsa J" uniqKey="Christiansen A" first="Ailsa J." last="Christiansen">Ailsa J. Christiansen</name><name sortKey="Detmar, Michael" sort="Detmar, Michael" uniqKey="Detmar M" first="Michael" last="Detmar">Michael Detmar</name><name sortKey="Halin, Cornelia" sort="Halin, Cornelia" uniqKey="Halin C" first="Cornelia" last="Halin">Cornelia Halin</name><name sortKey="Proulx, Steven T" sort="Proulx, Steven T" uniqKey="Proulx S" first="Steven T." last="Proulx">Steven T. Proulx</name><name sortKey="Seidel, Catharina D" sort="Seidel, Catharina D" uniqKey="Seidel C" first="Catharina D." last="Seidel">Catharina D. Seidel</name><name sortKey="Teijeira, Alvaro" sort="Teijeira, Alvaro" uniqKey="Teijeira A" first="Alvaro" last="Teijeira">Alvaro Teijeira</name></country><country name="Autriche"><region name="Vienne (Autriche)"><name sortKey="Rulicke, Thomas" sort="Rulicke, Thomas" uniqKey="Rulicke T" first="Thomas" last="Rülicke">Thomas Rülicke</name></region></country><country name="Suède"><region name="Svealand"><name sortKey="M Kinen, Taija" sort="M Kinen, Taija" uniqKey="M Kinen T" first="Taija" last="M Kinen">Taija M Kinen</name></region></country><country name="Allemagne"><region name="Rhénanie-du-Nord-Westphalie"><name sortKey="H Gerling, Rene" sort="H Gerling, Rene" uniqKey="H Gerling R" first="René" last="H Gerling">René H Gerling</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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