Defective remodeling and maturation of the lymphatic vasculature in Angiopoietin-2 deficient mice
Identifieur interne : 002767 ( Pmc/Corpus ); précédent : 002766; suivant : 002768Defective remodeling and maturation of the lymphatic vasculature in Angiopoietin-2 deficient mice
Auteurs : Michael Dellinger ; Robert Hunter ; Michael Bernas ; Nicholas Gale ; George Yancopoulos ; Robert Erickson ; Marlys WitteSource :
- Developmental biology [ 0012-1606 ] ; 2008.
Abstract
Molecular mechanisms regulating the remodeling of the lymphatic vasculature from an immature plexus of vessels to a hierarchal network of initial and collecting lymphatics are not well understood. One gene thought to be important for this process is Angiopoietin-2 (Ang-2).
Url:
DOI: 10.1016/j.ydbio.2008.04.024
PubMed: 18514180
PubMed Central: 2536689
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PMC:2536689Le document en format XML
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<author><name sortKey="Dellinger, Michael" sort="Dellinger, Michael" uniqKey="Dellinger M" first="Michael" last="Dellinger">Michael Dellinger</name>
<affiliation><nlm:aff id="A1">Department of Molecular and Cellular Biology, The University of Arizona, Tucson, AZ</nlm:aff>
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<author><name sortKey="Hunter, Robert" sort="Hunter, Robert" uniqKey="Hunter R" first="Robert" last="Hunter">Robert Hunter</name>
<affiliation><nlm:aff id="A2"> Department of Surgery, The University of Arizona, Tucson, AZ</nlm:aff>
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<author><name sortKey="Bernas, Michael" sort="Bernas, Michael" uniqKey="Bernas M" first="Michael" last="Bernas">Michael Bernas</name>
<affiliation><nlm:aff id="A2"> Department of Surgery, The University of Arizona, Tucson, AZ</nlm:aff>
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<author><name sortKey="Gale, Nicholas" sort="Gale, Nicholas" uniqKey="Gale N" first="Nicholas" last="Gale">Nicholas Gale</name>
<affiliation><nlm:aff id="A4"> Regeneron Pharmaceuticals, Inc., Tarrytown, NY</nlm:aff>
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<author><name sortKey="Yancopoulos, George" sort="Yancopoulos, George" uniqKey="Yancopoulos G" first="George" last="Yancopoulos">George Yancopoulos</name>
<affiliation><nlm:aff id="A4"> Regeneron Pharmaceuticals, Inc., Tarrytown, NY</nlm:aff>
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<author><name sortKey="Erickson, Robert" sort="Erickson, Robert" uniqKey="Erickson R" first="Robert" last="Erickson">Robert Erickson</name>
<affiliation><nlm:aff id="A1">Department of Molecular and Cellular Biology, The University of Arizona, Tucson, AZ</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Department of Pediatrics, The University of Arizona, Tucson, AZ</nlm:aff>
</affiliation>
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<author><name sortKey="Witte, Marlys" sort="Witte, Marlys" uniqKey="Witte M" first="Marlys" last="Witte">Marlys Witte</name>
<affiliation><nlm:aff id="A2"> Department of Surgery, The University of Arizona, Tucson, AZ</nlm:aff>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Defective remodeling and maturation of the lymphatic vasculature in Angiopoietin-2 deficient mice</title>
<author><name sortKey="Dellinger, Michael" sort="Dellinger, Michael" uniqKey="Dellinger M" first="Michael" last="Dellinger">Michael Dellinger</name>
<affiliation><nlm:aff id="A1">Department of Molecular and Cellular Biology, The University of Arizona, Tucson, AZ</nlm:aff>
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<author><name sortKey="Hunter, Robert" sort="Hunter, Robert" uniqKey="Hunter R" first="Robert" last="Hunter">Robert Hunter</name>
<affiliation><nlm:aff id="A2"> Department of Surgery, The University of Arizona, Tucson, AZ</nlm:aff>
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<author><name sortKey="Bernas, Michael" sort="Bernas, Michael" uniqKey="Bernas M" first="Michael" last="Bernas">Michael Bernas</name>
<affiliation><nlm:aff id="A2"> Department of Surgery, The University of Arizona, Tucson, AZ</nlm:aff>
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<author><name sortKey="Gale, Nicholas" sort="Gale, Nicholas" uniqKey="Gale N" first="Nicholas" last="Gale">Nicholas Gale</name>
<affiliation><nlm:aff id="A4"> Regeneron Pharmaceuticals, Inc., Tarrytown, NY</nlm:aff>
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<author><name sortKey="Yancopoulos, George" sort="Yancopoulos, George" uniqKey="Yancopoulos G" first="George" last="Yancopoulos">George Yancopoulos</name>
<affiliation><nlm:aff id="A4"> Regeneron Pharmaceuticals, Inc., Tarrytown, NY</nlm:aff>
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<author><name sortKey="Erickson, Robert" sort="Erickson, Robert" uniqKey="Erickson R" first="Robert" last="Erickson">Robert Erickson</name>
<affiliation><nlm:aff id="A1">Department of Molecular and Cellular Biology, The University of Arizona, Tucson, AZ</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Department of Pediatrics, The University of Arizona, Tucson, AZ</nlm:aff>
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<author><name sortKey="Witte, Marlys" sort="Witte, Marlys" uniqKey="Witte M" first="Marlys" last="Witte">Marlys Witte</name>
<affiliation><nlm:aff id="A2"> Department of Surgery, The University of Arizona, Tucson, AZ</nlm:aff>
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<series><title level="j">Developmental biology</title>
<idno type="ISSN">0012-1606</idno>
<idno type="eISSN">1095-564X</idno>
<imprint><date when="2008">2008</date>
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<front><div type="abstract" xml:lang="en"><p id="P1">Molecular mechanisms regulating the remodeling of the lymphatic vasculature from an immature plexus of vessels to a hierarchal network of initial and collecting lymphatics are not well understood. One gene thought to be important for this process is Angiopoietin-2 (Ang-2). <italic>Ang2<sup>-/-</sup>
</italic>
mice have previously been reported to exhibit an abnormal lymphatic phenotype but the precise nature of the lymphatic defects and the underlying mechanisms have yet to be defined. Here we demonstrate by whole-mount immunofluorescence staining of ear skin and mesentery that lymphatic vessels in <italic>Ang2<sup>-/-</sup>
</italic>
mice fail to mature and do not exhibit a collecting vessel phenotype. Furthermore, dermal lymphatic vessels in <italic>Ang2<sup>-/-</sup>
</italic>
pups prematurely recruit smooth muscle cells and do not undergo proper postnatal remodeling. In contrast, <italic>Ang2</italic>
knockout <italic>Ang1</italic>
knock-in mice do develop a hierarchal lymphatic vasculature, suggesting that activation of Tie-2 is required for normal lymphatic development. Taken together, this work pinpoints a specific lymphatic defect of <italic>Ang2<sup>-/-</sup>
</italic>
mice and further defines the sequential steps in lymphatic vessel remodeling.</p>
</div>
</front>
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<pmc article-type="research-article" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">0372762</journal-id>
<journal-id journal-id-type="pubmed-jr-id">3389</journal-id>
<journal-id journal-id-type="nlm-ta">Dev Biol</journal-id>
<journal-title>Developmental biology</journal-title>
<issn pub-type="ppub">0012-1606</issn>
<issn pub-type="epub">1095-564X</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">18514180</article-id>
<article-id pub-id-type="pmc">2536689</article-id>
<article-id pub-id-type="doi">10.1016/j.ydbio.2008.04.024</article-id>
<article-id pub-id-type="manuscript">NIHMS59873</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Defective remodeling and maturation of the lymphatic vasculature in Angiopoietin-2 deficient mice</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Dellinger</surname>
<given-names>Michael</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hunter</surname>
<given-names>Robert</given-names>
</name>
<xref rid="A2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bernas</surname>
<given-names>Michael</given-names>
</name>
<xref rid="A2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gale</surname>
<given-names>Nicholas</given-names>
</name>
<xref rid="A4" ref-type="aff">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Yancopoulos</surname>
<given-names>George</given-names>
</name>
<xref rid="A4" ref-type="aff">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Erickson</surname>
<given-names>Robert</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="A3" ref-type="aff">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Witte</surname>
<given-names>Marlys</given-names>
</name>
<xref rid="A2" ref-type="aff">2</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Department of Molecular and Cellular Biology, The University of Arizona, Tucson, AZ</aff>
<aff id="A2"><label>2</label>
Department of Surgery, The University of Arizona, Tucson, AZ</aff>
<aff id="A3"><label>3</label>
Department of Pediatrics, The University of Arizona, Tucson, AZ</aff>
<aff id="A4"><label>4</label>
Regeneron Pharmaceuticals, Inc., Tarrytown, NY</aff>
<author-notes><corresp id="FN1">Corresponding author: Marlys Hearst Witte, MD, Professor of Surgery, University of Arizona College of Medicine, 1501 N. Campbell Avenue, Room 4406, P.O. Box 245200, Tucson, AZ USA 85724-5200, Telephone: 520-626-6118, Fax: 520-626-0822, e-mail: <email>lymph@u.arizona.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>31</day>
<month>7</month>
<year>2008</year>
</pub-date>
<pub-date pub-type="epub"><day>27</day>
<month>4</month>
<year>2008</year>
</pub-date>
<pub-date pub-type="ppub"><day>15</day>
<month>7</month>
<year>2008</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>15</day>
<month>7</month>
<year>2009</year>
</pub-date>
<volume>319</volume>
<issue>2</issue>
<fpage>309</fpage>
<lpage>320</lpage>
<abstract><p id="P1">Molecular mechanisms regulating the remodeling of the lymphatic vasculature from an immature plexus of vessels to a hierarchal network of initial and collecting lymphatics are not well understood. One gene thought to be important for this process is Angiopoietin-2 (Ang-2). <italic>Ang2<sup>-/-</sup>
</italic>
mice have previously been reported to exhibit an abnormal lymphatic phenotype but the precise nature of the lymphatic defects and the underlying mechanisms have yet to be defined. Here we demonstrate by whole-mount immunofluorescence staining of ear skin and mesentery that lymphatic vessels in <italic>Ang2<sup>-/-</sup>
</italic>
mice fail to mature and do not exhibit a collecting vessel phenotype. Furthermore, dermal lymphatic vessels in <italic>Ang2<sup>-/-</sup>
</italic>
pups prematurely recruit smooth muscle cells and do not undergo proper postnatal remodeling. In contrast, <italic>Ang2</italic>
knockout <italic>Ang1</italic>
knock-in mice do develop a hierarchal lymphatic vasculature, suggesting that activation of Tie-2 is required for normal lymphatic development. Taken together, this work pinpoints a specific lymphatic defect of <italic>Ang2<sup>-/-</sup>
</italic>
mice and further defines the sequential steps in lymphatic vessel remodeling.</p>
</abstract>
<kwd-group><kwd>Ang2</kwd>
<kwd>Angpt2</kwd>
<kwd>Angiopoietin-2</kwd>
<kwd>Ang2 knockout mice</kwd>
<kwd>Angiopoietin-1</kwd>
<kwd>Tie2</kwd>
<kwd>lymphedema</kwd>
<kwd>lymphangiogenesis</kwd>
<kwd>lymphatic development</kwd>
<kwd>lymphatic remodeling</kwd>
</kwd-group>
<contract-num rid="HL1">R01 HL071206-04</contract-num>
<contract-sponsor id="HL1">National Heart, Lung, and Blood Institute : NHLBI</contract-sponsor>
</article-meta>
</front>
</pmc>
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