{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:52:08Z","timestamp":1791193928214,"version":"4.1.0"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"11","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,3,17]]},"abstract":"<jats:p>\n                    Retinoic acid (RA) receptors (RARs) \u03b1, \u03b2, and \u03b3 heterodimerized with rexinoid receptors (RXRs) \u03b1, \u03b2, and \u03b3 mediate the RA signal. To analyze the contribution of the transcriptional activity of RXR\u03b1, the main RXR during embryogenesis, we have engineered a mouse line harboring a transcriptionally silent RXR\u03b1 mutant that lacks the activation functions AF1 and AF2. All homozygous mutants (\n                    <jats:italic>\n                      Rxra\n                      <jats:sup>afo<\/jats:sup>\n                    <\/jats:italic>\n                    ) display the ocular defects previously observed in compound\n                    <jats:italic>Rar<\/jats:italic>\n                    -null and\n                    <jats:italic>Rxra<\/jats:italic>\n                    \/\n                    <jats:italic>Rar<\/jats:italic>\n                    -null mutants, thus demonstrating that a transcriptionally active RXR\u03b1 is required during eye development. In contrast, the vast majority of\n                    <jats:italic>\n                      Rxra\n                      <jats:sup>afo<\/jats:sup>\n                    <\/jats:italic>\n                    fetuses do not display the\n                    <jats:italic>Rxra<\/jats:italic>\n                    -null mutant hypoplasia of the myocardium, thus demonstrating that RXR\u03b1 can act as a transcriptionally silent heterodimerization partner. Similarly, a transcriptionally silent RXR\u03b1 mutant can support early embryogenesis, as\n                    <jats:italic>\n                      Rxra\n                      <jats:sup>afo<\/jats:sup>\n                      \/Rxrb\n                    <\/jats:italic>\n                    -null embryos display a normal morphology, contrasting with the severe malformations exhibited by compound\n                    <jats:italic>Rxra<\/jats:italic>\n                    \/\n                    <jats:italic>Rxrb<\/jats:italic>\n                    -null embryos. Along the same line, we show that a silent RXR\u03b1 mutant is sufficient to allow the initial formation of the placental labyrinth, whereas later steps of trophoblast cell differentiation critically requires the AF2, but not the AF1, function of RXR\u03b1.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0813143106","type":"journal-article","created":{"date-parts":[[2009,3,2]],"date-time":"2009-03-02T21:43:19Z","timestamp":1236030199000},"page":"4272-4277","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":48,"title":["A transcriptionally silent RXR\u03b1 supports early embryonic morphogenesis and heart development"],"prefix":"10.1073","volume":"106","author":[{"given":"B\u00e9n\u00e9dicte","family":"Mascrez","sequence":"first","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique Unit\u00e9 Mixte de Recherche 7104, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U964, University Louis Pasteur de Strasbourg, BP10142, 67404 Illkirch Cedex, CU de Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert B.","family":"Ghyselinck","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique Unit\u00e9 Mixte de Recherche 7104, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U964, University Louis Pasteur de Strasbourg, BP10142, 67404 Illkirch Cedex, CU 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 Unit\u00e9 Mixte de Recherche 7104, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U964, University Louis Pasteur de Strasbourg, BP10142, 67404 Illkirch Cedex, CU de Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Mark","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique Unit\u00e9 Mixte de Recherche 7104, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U964, University Louis Pasteur de Strasbourg, BP10142, 67404 Illkirch Cedex, CU de Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,3,17]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.10.9.8801176"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2005-0125"},{"key":"e_1_3_3_3_2","volume-title":"The Nuclear Receptor Facts Book","author":"Laudet V","year":"2002","unstructured":"V Laudet, H Gronemeyer The Nuclear Receptor Facts Book (Academic, London, 2002)."},{"key":"e_1_3_3_4_2","first-page":"909","article-title":"F9 embryocarcinoma cells: A cell autonomous model to study the functional selectivity of RARs and RXRs in retinoid signaling","volume":"16","author":"Rochette-Egly C","year":"2001","unstructured":"C Rochette-Egly, P Chambon, F9 embryocarcinoma cells: A cell autonomous model to study the functional selectivity of RARs and RXRs in retinoid signaling. 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