{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:08:08Z","timestamp":1791112088442,"version":"4.1.0"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,4,16]]},"abstract":"<jats:p>\n                    TRAF4 belongs to the tumor necrosis factor receptor-associated factor (TRAF) family of proteins but, unlike other family members, has not yet been clearly associated to any specific receptor or signaling pathway. To investigate the biological function of TRAF4, we have generated\n                    <jats:italic>traf4<\/jats:italic>\n                    -deficient mice by gene disruption. The\n                    <jats:italic>traf4<\/jats:italic>\n                    gene mutation is embryonic lethal but with great individual variation, as approximately one third of the homozygous mutant embryos died\n                    <jats:italic>in utero<\/jats:italic>\n                    around embryonic day 14, whereas the others reach adulthood. Surviving mutant mice manifest numerous developmental abnormalities; notably, 100% of homozygous mutant mice suffer respiratory disorder and wheezing caused by tracheal ring disruption. Additional malformations concern mainly the axial skeleton, as the ribs, sternum, tail, and vertebral arches are affected, with various degrees of penetrance.\n                    <jats:italic>Traf4<\/jats:italic>\n                    -deficient mice also exhibit a high incidence of spina bifida, a defect likened to neural tube defects (NTD) that are common congenital malformations in humans. Altogether, our results demonstrate that TRAF4 is required during embryogenesis in key biological processes including the formation of the trachea, the development of the axial skeleton, and the closure of the neural tube. Considering the normal expression pattern of TRAF4 in neural tissues, we can conclude that TRAF4 participates in neurulation\n                    <jats:italic>in vivo<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1073\/pnas.052124799","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:45:09Z","timestamp":1027680309000},"page":"5585-5590","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":93,"title":["Impaired neural tube closure, axial skeleton malformations, and tracheal ring disruption in TRAF4-deficient mice"],"prefix":"10.1073","volume":"99","author":[{"given":"Catherine H.","family":"R\u00e9gnier","sequence":"first","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique Unit\u00e9 Propre de Recherche 6520\/Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unit\u00e9 184\/Universit\u00e9 Louis Pasteur, B.P. 163, 67404 Illkirch Cedex, France; and Service d'Anatomie Pathologique G\u00e9n\u00e9rale, Centre Hospitalier Universitaire de Hautepierre, 67098 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9gis","family":"Masson","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique Unit\u00e9 Propre de Recherche 6520\/Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unit\u00e9 184\/Universit\u00e9 Louis Pasteur, B.P. 163, 67404 Illkirch Cedex, France; and Service d'Anatomie Pathologique G\u00e9n\u00e9rale, Centre Hospitalier Universitaire de Hautepierre, 67098 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Kedinger","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique Unit\u00e9 Propre de Recherche 6520\/Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unit\u00e9 184\/Universit\u00e9 Louis Pasteur, B.P. 163, 67404 Illkirch Cedex, France; 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