Flt1/VEGFR1 heterozygosity causes transient embryonic edema
Identifieur interne : 001549 ( Main/Exploration ); précédent : 001548; suivant : 001550Flt1/VEGFR1 heterozygosity causes transient embryonic edema
Auteurs : Yasunori Otowa [Japon] ; Kazumasa Moriwaki [Japon] ; Keigo Sano [Japon] ; Masanori Shirakabe [Japon] ; Shigenobu Yonemura [Japon] ; Masabumi Shibuya [Japon] ; Janet Rossant [Canada] ; Toshio Suda [Singapour, Japon] ; Yoshihiro Kakeji [Japon] ; Masanori Hirashima [Japon]Source :
- Scientific Reports [ 2045-2322 ] ; 2016.
Abstract
Vascular endothelial growth factor-A is a major player in vascular development and a potent vascular permeability factor under physiological and pathological conditions by binding to a decoy receptor Flt1 and its primary receptor Flk1. In this study, we show that
Url:
DOI: 10.1038/srep27186
PubMed: 27251772
PubMed Central: 4890026
Affiliations:
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nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Moriwaki, Kazumasa" sort="Moriwaki, Kazumasa" uniqKey="Moriwaki K" first="Kazumasa" last="Moriwaki">Kazumasa Moriwaki</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Vascular Biology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine</institution>, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sano, Keigo" sort="Sano, Keigo" uniqKey="Sano K" first="Keigo" last="Sano">Keigo Sano</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Vascular Biology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine</institution>, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 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Technologies</institution>, 2-3-3, Minatojima-minamimachi, Kobe, Hyogo 650-0047,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shibuya, Masabumi" sort="Shibuya, Masabumi" uniqKey="Shibuya M" first="Masabumi" last="Shibuya">Masabumi Shibuya</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Institute of Physiology and Medicine, Jobu University</institution>, 270-1 Shinmachi, Takasaki, Gunma 370-1393,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Rossant, Janet" sort="Rossant, Janet" uniqKey="Rossant J" first="Janet" last="Rossant">Janet Rossant</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Peter Gilgan Centre for Research and Learning</institution>, 686 Bay Street, Toronto, Ontario, M5G0A4<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Suda, Toshio" sort="Suda, Toshio" uniqKey="Suda T" first="Toshio" last="Suda">Toshio Suda</name><affiliation wicri:level="1"><nlm:aff id="a6"><institution>Cancer Science Institute, National University of Singapore, Center for Translational Medicine</institution>, 14 Medical Drive, #12-01, 117599,<country>Singapore</country></nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a7"><institution>International Research Center for Medical Sciences, Kumamoto University</institution>, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kakeji, Yoshihiro" sort="Kakeji, Yoshihiro" uniqKey="Kakeji Y" first="Yoshihiro" last="Kakeji">Yoshihiro Kakeji</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine</institution>, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hirashima, Masanori" sort="Hirashima, Masanori" uniqKey="Hirashima M" first="Masanori" last="Hirashima">Masanori Hirashima</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Vascular Biology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine</institution>, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 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id="a2"><institution>Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine</institution>, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Moriwaki, Kazumasa" sort="Moriwaki, Kazumasa" uniqKey="Moriwaki K" first="Kazumasa" last="Moriwaki">Kazumasa Moriwaki</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Vascular Biology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine</institution>, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sano, Keigo" sort="Sano, Keigo" uniqKey="Sano K" first="Keigo" last="Sano">Keigo Sano</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Vascular Biology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine</institution>, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shirakabe, Masanori" sort="Shirakabe, Masanori" uniqKey="Shirakabe M" first="Masanori" last="Shirakabe">Masanori Shirakabe</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Vascular Biology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine</institution>, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yonemura, Shigenobu" sort="Yonemura, Shigenobu" uniqKey="Yonemura S" first="Shigenobu" last="Yonemura">Shigenobu Yonemura</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Ultrastructural Research Team, RIKEN Center for Life Science Technologies</institution>, 2-3-3, Minatojima-minamimachi, Kobe, Hyogo 650-0047,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shibuya, Masabumi" sort="Shibuya, Masabumi" uniqKey="Shibuya M" first="Masabumi" last="Shibuya">Masabumi Shibuya</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Institute of Physiology and Medicine, Jobu University</institution>, 270-1 Shinmachi, Takasaki, Gunma 370-1393,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Rossant, Janet" sort="Rossant, Janet" uniqKey="Rossant J" first="Janet" last="Rossant">Janet Rossant</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Peter Gilgan Centre for Research and Learning</institution>, 686 Bay Street, Toronto, Ontario, M5G0A4<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Suda, Toshio" sort="Suda, Toshio" uniqKey="Suda T" first="Toshio" last="Suda">Toshio Suda</name><affiliation wicri:level="1"><nlm:aff id="a6"><institution>Cancer Science Institute, National University of Singapore, Center for Translational Medicine</institution>, 14 Medical Drive, #12-01, 117599,<country>Singapore</country></nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a7"><institution>International Research Center for Medical Sciences, Kumamoto University</institution>, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kakeji, Yoshihiro" sort="Kakeji, Yoshihiro" uniqKey="Kakeji Y" first="Yoshihiro" last="Kakeji">Yoshihiro Kakeji</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine</institution>, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hirashima, Masanori" sort="Hirashima, Masanori" uniqKey="Hirashima M" first="Masanori" last="Hirashima">Masanori Hirashima</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Division of Vascular Biology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine</institution>, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Vascular endothelial growth factor-A is a major player in vascular development and a potent vascular permeability factor under physiological and pathological conditions by binding to a decoy receptor Flt1 and its primary receptor Flk1. In this study, we show that <italic>Flt1</italic> heterozygous (<italic>Flt1</italic><sup>+/−</sup>) mouse embryos grow up to adult without life-threatening abnormalities but exhibit a transient embryonic edema around the nuchal and back regions, which is reminiscent of increased nuchal translucency in human fetuses. Vascular permeability is enhanced and an intricate infolding of the plasma membrane and huge vesicle-like structures are seen in <italic>Flt1</italic><sup>+/−</sup> capillary endothelial cells. Flk1 tyrosine phosphorylation is elevated in <italic>Flt1</italic><sup>+/−</sup> embryos, but <italic>Flk1</italic> heterozygosity does not suppress embryonic edema caused by <italic>Flt1</italic> heterozygosity. When <italic>Flt1</italic> mutants are crossed with <italic>Aspp1</italic><sup>−/−</sup> mice which exhibit a transient embryonic edema with delayed formation and dysfunction of lymphatic vessels, only 5.7% of <italic>Flt1</italic><sup>+/−</sup>; <italic>Aspp1</italic><sup>−/−</sup> mice survive, compared to expected ratio (25%). Our results demonstrate that <italic>Flt1</italic> heterozygosity causes a transient embryonic edema and can be a risk factor for embryonic lethality in combination with other mutations causing non-lethal vascular phenotype.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Keck, P J" uniqKey="Keck P">P. J. Keck</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leung, D W" uniqKey="Leung D">D. W. Leung</name></author><author><name sortKey="Cachianes, G" uniqKey="Cachianes G">G. Cachianes</name></author><author><name sortKey="Kuang, W J" uniqKey="Kuang W">W. J. 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Haak</name></author><author><name sortKey="Van Vugt, J M" uniqKey="Van Vugt J">J. M. van Vugt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Souka, A P" uniqKey="Souka A">A. P. Souka</name></author><author><name sortKey="Von Kaisenberg, C S" uniqKey="Von Kaisenberg C">C. S. Von Kaisenberg</name></author><author><name sortKey="Hyett, J A" uniqKey="Hyett J">J. A. Hyett</name></author><author><name sortKey="Sonek, J D" uniqKey="Sonek J">J. D. Sonek</name></author><author><name sortKey="Nicolaides, K H" uniqKey="Nicolaides K">K. H. Nicolaides</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hirashima, M" uniqKey="Hirashima M">M. Hirashima</name></author><author><name sortKey="Lu, Y" uniqKey="Lu Y">Y. Lu</name></author><author><name sortKey="Byers, L" uniqKey="Byers L">L. Byers</name></author><author><name sortKey="Rossant, J" uniqKey="Rossant J">J. Rossant</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Morisada, T" uniqKey="Morisada T">T. Morisada</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thurston, G" uniqKey="Thurston G">G. Thurston</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Canada</li><li>Japon</li><li>Singapour</li></country></list><tree><country name="Japon"><noRegion><name sortKey="Otowa, Yasunori" sort="Otowa, Yasunori" uniqKey="Otowa Y" first="Yasunori" last="Otowa">Yasunori Otowa</name></noRegion><name sortKey="Hirashima, Masanori" sort="Hirashima, Masanori" uniqKey="Hirashima M" first="Masanori" last="Hirashima">Masanori Hirashima</name><name sortKey="Kakeji, Yoshihiro" sort="Kakeji, Yoshihiro" uniqKey="Kakeji Y" first="Yoshihiro" last="Kakeji">Yoshihiro Kakeji</name><name sortKey="Moriwaki, Kazumasa" sort="Moriwaki, Kazumasa" uniqKey="Moriwaki K" first="Kazumasa" last="Moriwaki">Kazumasa Moriwaki</name><name sortKey="Otowa, Yasunori" sort="Otowa, Yasunori" uniqKey="Otowa Y" first="Yasunori" last="Otowa">Yasunori Otowa</name><name sortKey="Sano, Keigo" sort="Sano, Keigo" uniqKey="Sano K" first="Keigo" last="Sano">Keigo Sano</name><name sortKey="Shibuya, Masabumi" sort="Shibuya, Masabumi" uniqKey="Shibuya M" first="Masabumi" last="Shibuya">Masabumi Shibuya</name><name sortKey="Shirakabe, Masanori" sort="Shirakabe, Masanori" uniqKey="Shirakabe M" first="Masanori" last="Shirakabe">Masanori Shirakabe</name><name sortKey="Suda, Toshio" sort="Suda, Toshio" uniqKey="Suda T" first="Toshio" last="Suda">Toshio Suda</name><name sortKey="Yonemura, Shigenobu" sort="Yonemura, Shigenobu" uniqKey="Yonemura S" first="Shigenobu" last="Yonemura">Shigenobu Yonemura</name></country><country name="Canada"><noRegion><name sortKey="Rossant, Janet" sort="Rossant, Janet" uniqKey="Rossant J" first="Janet" last="Rossant">Janet Rossant</name></noRegion></country><country name="Singapour"><noRegion><name sortKey="Suda, Toshio" sort="Suda, Toshio" uniqKey="Suda T" first="Toshio" last="Suda">Toshio Suda</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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