{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:45:22Z","timestamp":1791308722299,"version":"4.3.1"},"reference-count":45,"publisher":"The Company of Biologists","issue":"19","license":[{"start":{"date-parts":[[2000,10,1]],"date-time":"2000-10-01T00:00:00Z","timestamp":970358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>In order to reveal the biological function(s) of the gap-junction protein connexin 45 (Cx45), we generated Cx45-deficient mice with targeted replacement of the Cx45-coding region with the lacZ reporter gene. Heterozygous Cx45+\/\u2212 mice showed strong expression of the reporter gene in vascular and visceral smooth muscle cells. Cx45-deficient embryos exhibited striking abnormalities in vascular development and died between embryonic day (E) 9.5 and 10.5. Differentiation and positioning of endothelial cells appeared to be normal, but subsequent development of blood vessels revealed impaired formation of vascular trees in the yolk sac, impaired allantoic mesenchymal ingrowth and capillary formation in the labyrinthine part of the placenta, and arrest of arterial growth, including a failure to develop a smooth muscle layer surrounding the major arteries of the embryo proper. As a consequence, the hearts of most Cx45-deficient embryos were dilated. The abnormal development of the vasculature in the yolk sac of Cx45\u2212\/\u2212 embryos could be caused by defective TGF\u03b2 signalling, as the amount of TGF \u03b21 protein in the epithelial layer of the yolk sac was largely decreased in the E9.5 Cx45\u2212\/\u2212 embryo, compared with the wild-type embryo. The defective vascular development was accompanied by massive apoptosis, which began in some embryos at E8.5 and was abundant in virtually all tissues of the embryos at E9.5. We conclude that in Cx45\u2212\/\u2212 embryos, vasculogenesis was normal, but subsequent transformation into mature vessels was interrupted. Development of different types of vessels was impaired to a varying extent, which possibly reflects the complementation by other connexin(s).<\/jats:p>","DOI":"10.1242\/dev.127.19.4179","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T04:16:11Z","timestamp":1619410571000},"page":"4179-4193","source":"Crossref","is-referenced-by-count":310,"title":["Defective vascular development in connexin 45-deficient mice"],"prefix":"10.1242","volume":"127","author":[{"given":"Olaf","family":"Kr\u00fcger","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Genetik 1 , Abt. Molekulargenetik, Universit\u00e4t Bonn, 53117 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Plum","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Genetik 1 , Abt. Molekulargenetik, Universit\u00e4t Bonn, 53117 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Sun","family":"Kim","sequence":"additional","affiliation":[{"name":"Academic Medical Center, University of Amsterdam 2 Department of Anatomy and Embryology , , 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Winterhager","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Anatomie, Universit\u00e4t Essen 3 , 45122 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Maxeiner","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Genetik 1 , Abt. Molekulargenetik, Universit\u00e4t Bonn, 53117 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaby","family":"Hallas","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Genetik 1 , Abt. 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