{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T21:56:53Z","timestamp":1791064613088,"version":"4.1.0"},"reference-count":52,"publisher":"The Company of Biologists","issue":"6","license":[{"start":{"date-parts":[[1999,3,15]],"date-time":"1999-03-15T00:00:00Z","timestamp":921456000000},"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":[[1999,3,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>We employed two independent approaches to inactivate the angiogenic protein VEGF in newborn mice: inducible, Cre-loxP-mediated gene targeting, or administration of mFlt(1-3)-IgG, a soluble VEGF receptor chimeric protein. Partial inhibition of VEGF achieved by inducible gene targeting resulted in increased mortality, stunted body growth and impaired organ development, most notably of the liver. Administration of mFlt(1-3)-IgG, which achieves a higher degree of VEGF inhibition, resulted in nearly complete growth arrest and lethality. Ultrastructural analysis documented alterations in endothelial and other cell types. Histological and biochemical changes consistent with liver and renal failure were observed. Endothelial cells isolated from the liver of mFlt(1-3)-IgG-treated neonates demonstrated an increased apoptotic index, indicating that VEGF is required not only for proliferation but also for survival of endothelial cells. However, such treatment resulted in less significant alterations as the animal matured, and the dependence on VEGF was eventually lost some time after the fourth postnatal week. Administration of mFlt(1-3)-IgG to juvenile mice failed to induce apoptosis in liver endothelial cells. Thus, VEGF is essential for growth and survival in early postnatal life. However, in the fully developed animal, VEGF is likely to be involved primarily in active angiogenesis processes such as corpus luteum development.<\/jats:p>","DOI":"10.1242\/dev.126.6.1149","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T03:57:25Z","timestamp":1619409445000},"page":"1149-1159","source":"Crossref","is-referenced-by-count":753,"title":["VEGF is required for growth and survival in neonatal mice"],"prefix":"10.1242","volume":"126","author":[{"given":"Hans-Peter","family":"Gerber","sequence":"first","affiliation":[{"name":"Departments of Cardiovascular Research and Pathology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth J.","family":"Hillan","sequence":"additional","affiliation":[{"name":"Departments of Cardiovascular Research and Pathology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Departments of Cardiovascular Research and Pathology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Kowalski","sequence":"additional","affiliation":[{"name":"Departments of Cardiovascular Research and Pathology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilbert-Andre","family":"Keller","sequence":"additional","affiliation":[{"name":"Departments of Cardiovascular Research and Pathology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Rangell","sequence":"additional","affiliation":[{"name":"Departments of Cardiovascular Research and Pathology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara D.","family":"Wright","sequence":"additional","affiliation":[{"name":"Departments of Cardiovascular Research and Pathology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freddy","family":"Radtke","sequence":"additional","affiliation":[{"name":"Departments of Cardiovascular Research and Pathology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Aguet","sequence":"additional","affiliation":[{"name":"Departments of Cardiovascular Research and Pathology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Napoleone","family":"Ferrara","sequence":"additional","affiliation":[{"name":"Departments of Cardiovascular Research and Pathology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1999,3,15]]},"reference":[{"key":"2023090516054091200_DEVELOP_126_6_1149C1","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1038\/nm1095-1024","article-title":"Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity","volume":"1","author":"Alon","year":"1995","journal-title":"Nat. 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