{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T19:04:54Z","timestamp":1748977494025},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,5,18]],"date-time":"2013-05-18T00:00:00Z","timestamp":1368835200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J Oral Sciences"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:p>The detection of gene mutations in patients with congenitally missing teeth is not very complicated; however, proving causality is often quite difficult. Here, we report the detection of a substitution mutation, A42P, within the prodomain of bone morphogenetic protein 4 (<jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>4) in a small family with tooth agenesis and describe a functional alteration that may be responsible for the tooth phenotype. As <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>4 is essential for the development of teeth and also for many other organs, it would be of considerable interest to find a <jats:italic><jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>4<\/jats:italic> mutation that is associated only with tooth agenesis. Our in vitro investigations revealed that the A42P mutation neither affected processing and secretion of <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>4 nor altered functional properties, such as the induction of alkaline phosphatase or signaling through Smad1\/5\/8 phosphorylation by the mature <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>4 ligand. However, immunofluorescence staining revealed that the prodomains of <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>4 which harbor the A42P substitution form fibrillar structures around transfected cells in culture and that this fibrillar network is significantly decreased when mutant prodomains are expressed. Our finding suggests that in vivo, <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>4 prodomain behavior might also be altered by the mutation and could influence storage or transport of mature <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>4 in the extracellular matrix of the developing tooth.<\/jats:p>","DOI":"10.1111\/eos.12055","type":"journal-article","created":{"date-parts":[[2013,5,18]],"date-time":"2013-05-18T21:15:03Z","timestamp":1368911703000},"page":"313-318","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Functional evaluation of a novel tooth agenesis\u2010associated bone morphogenetic protein 4 prodomain mutation"],"prefix":"10.1111","volume":"121","author":[{"given":"Yanyu","family":"Huang","sequence":"first","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei\u2010MOST) Key Laboratory of Oral Biomedicine Ministry of Education School &amp; Hospital of Stomatology Wuhan University Wuhan China"},{"name":"Biomedical Sciences Baylor College of Dentistry Texas A&amp;M Health Science Center Dallas TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongbo","family":"Lu","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Baylor College of Dentistry Texas A&amp;M Health Science Center Dallas TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele","family":"Mues","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Baylor College of Dentistry Texas A&amp;M Health Science Center Dallas TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Baylor College of Dentistry Texas A&amp;M Health Science Center Dallas TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Bonds","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Baylor College of Dentistry Texas A&amp;M Health Science Center Dallas TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rena","family":"D'Souza","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Baylor College of Dentistry Texas A&amp;M Health Science Center Dallas TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,5,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-5406(00)70173-9"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910808700715"},{"key":"e_1_2_7_4_1","first-page":"479","article-title":"Tooth morphology in rubella syndrome children","volume":"42","author":"Gullikson JS","year":"1975","journal-title":"ASDC J Dent Child"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2012-100750"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33840"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1086\/386293"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32801"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-6343.2007.00407.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0494-348"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.17.2735"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(05)80083-2"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-011-0968-y"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.02.002"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.1712"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.16.4735"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02368"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M605330200"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707820200"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10152"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-009-1287-6"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.144.1.139"},{"key":"e_1_2_7_23_1","doi-asserted-by":"crossref","first-page":"2797","DOI":"10.1101\/gad.940001","article-title":"The activity and signaling range of mature BMP\u20104 is regulated by sequential cleavage at two sites within the prodomain of the precursor","volume":"15","author":"Cui Y","year":"2001","journal-title":"Genes Dev"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.028506"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.127.6.1755"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2005.04.019"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.03.008"}],"container-title":["European Journal of Oral Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Feos.12055","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/eos.12055","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T02:53:13Z","timestamp":1696301593000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/eos.12055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,18]]},"references-count":26,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,8]]}},"alternative-id":["10.1111\/eos.12055"],"URL":"https:\/\/doi.org\/10.1111\/eos.12055","archive":["Portico"],"relation":{},"ISSN":["0909-8836","1600-0722"],"issn-type":[{"value":"0909-8836","type":"print"},{"value":"1600-0722","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5,18]]},"assertion":[{"value":"2013-04-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-05-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}