{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:44:42Z","timestamp":1791308682194,"version":"4.3.1"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,2,18]]},"abstract":"<jats:p>\n                    Retinoic acid (RA), the active derivative of vitamin A, is involved in various developmental and homeostatic processes. To define whether certain developmental events are particularly sensitive to a decrease in embryonic RA levels, we generated mice bearing a hypomorphic allele of the RA-synthesizing enzyme\n                    <jats:italic>Raldh2<\/jats:italic>\n                    . The resulting mutant mice, which die perinatally, exhibit the features of the human DiGeorge syndrome (DGS) with heart outflow tract septation defects and anomalies of the aortic arch-derived head and neck arteries, laryngeal-tracheal cartilage defects, and thymus\/parathyroid aplasia or hypoplasia. Analysis of\n                    <jats:italic>Raldh2<\/jats:italic>\n                    hypomorph embryos reveal selective defects of the posterior (third to sixth) branchial arches, including absence or hypoplasia of the corresponding aortic arches and pharyngeal pouches, and local down-regulation of RA-target genes. Thus, a decreased level of embryonic RA (through genetic and\/or nutritional causes) could represent a major modifier of the expressivity of human 22q11del-associated DiGeorge\/velocardiofacial syndromes and, if severe enough, could on its own lead to the clinical features of the DiGeorge syndrome.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0437920100","type":"journal-article","created":{"date-parts":[[2003,2,18]],"date-time":"2003-02-18T15:04:50Z","timestamp":1045580690000},"page":"1763-1768","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":144,"title":["Decreased embryonic retinoic acid synthesis results in a DiGeorge syndrome phenotype in newborn mice"],"prefix":"10.1073","volume":"100","author":[{"given":"Julien","family":"Vermot","sequence":"first","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique\/Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale\/Universit\u00e9 Louis Pasteur\/Coll\u00e8ge de France, BP 10142, 67404 Illkirch Cedex, Communaut\u00e9 Urbaine de Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Niederreither","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique\/Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale\/Universit\u00e9 Louis Pasteur\/Coll\u00e8ge de France, BP 10142, 67404 Illkirch Cedex, Communaut\u00e9 Urbaine de Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marie","family":"Garnier","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique\/Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale\/Universit\u00e9 Louis Pasteur\/Coll\u00e8ge de France, BP 10142, 67404 Illkirch Cedex, Communaut\u00e9 Urbaine de Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Chambon","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique\/Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale\/Universit\u00e9 Louis Pasteur\/Coll\u00e8ge de France, BP 10142, 67404 Illkirch Cedex, Communaut\u00e9 Urbaine de Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Doll\u00e9","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique\/Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale\/Universit\u00e9 Louis Pasteur\/Coll\u00e8ge de France, BP 10142, 67404 Illkirch Cedex, Communaut\u00e9 Urbaine de Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2003,1,31]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.1994.tb01385.x"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.10.9.8801176"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(00)00303-8"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90202-3"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1000920202"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1996.0015h.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(00)00434-2"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(96)00653-3"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/7788"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.128.7.1019"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.1.75"},{"key":"e_1_3_3_12_2","first-page":"116","volume":"4","author":"DiGeorge A M","year":"1968","unstructured":"A M DiGeorge Birth Defects Orig Art Ser 4, 116\u2013121 (1968).","journal-title":"Birth Defects Orig Art Ser"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(79)80207-3"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.119.2.319"},{"key":"e_1_3_3_15_2","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1093\/oso\/9780199634156.003.0008","volume-title":"Gene Probes 2: A Practical Approach","author":"D\u00e9cimo D","year":"1995","unstructured":"D D\u00e9cimo, E Georges-Labouesse, P Doll\u00e9 Gene Probes 2: A Practical Approach, eds B D Hames, S J Higgins (Oxford Univ. 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