{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T18:39:48Z","timestamp":1757702388679,"version":"3.40.5"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T00:00:00Z","timestamp":1609977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005648","name":"American Association of Orthodontists Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005648","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Orthod Craniofacial Res"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine the functional effects of <jats:italic>ATF1, WNT10B<\/jats:italic> and <jats:italic>GREM2<\/jats:italic> gene variants identified in individuals with tooth agenesis (TA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Settings and sample population<\/jats:title><jats:p>Stem cells from human exfoliated deciduous teeth (SHED) were used as an in vitro model system to test the effect of TA\u2010associated variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Plasmid constructs containing reference and mutant alleles for <jats:italic>ATF1<\/jats:italic> rs11169552, <jats:italic>WNT10B<\/jats:italic> rs833843 and <jats:italic>GREM2<\/jats:italic> rs1414655 variants were transfected into SHED for functional characterization of variants. Allele\u2010specific changes in gene transcription activity, protein expression, cell migration and proliferation, and expression of additional tooth development genes (<jats:italic>MSX1, PAX9<\/jats:italic> and <jats:italic>AXIN2)<\/jats:italic> were evaluated. Data analyses were performed using Student's <jats:italic>t<\/jats:italic>\u2010test. <jats:italic>P<\/jats:italic>\u2010values\u00a0\u2264\u00a0.05 were considered statistically significant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mutant variants resulted in significantly decreased transcriptional activity of respective genes (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), although no changes in protein localization were noted. Expression of <jats:italic>MSX1<\/jats:italic> was significantly decreased in <jats:italic>ATF1\u2010<\/jats:italic> and <jats:italic>GREM2<\/jats:italic>\u2010mutant cells, whereas <jats:italic>PAX9<\/jats:italic> or <jats:italic>AXIN2<\/jats:italic> mRNA expression was not significantly altered. Mutant <jats:italic>WNT10B<\/jats:italic> had no significant effect on the expression of additional TA genes. <jats:italic>ATF1\u2010<\/jats:italic> and <jats:italic>GREM2<\/jats:italic>\u2010mutant cells presented increased cell migration. Cell proliferation was also affected with all three mutant alleles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results demonstrate that <jats:italic>ATF1, WNT10B<\/jats:italic> and <jats:italic>GREM2<\/jats:italic> mutant alleles have modulatory effects on gene\/protein function that may contribute to TA.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ocr.12462","type":"journal-article","created":{"date-parts":[[2020,12,24]],"date-time":"2020-12-24T16:34:18Z","timestamp":1608827658000},"page":"486-493","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Functional characterization of <i>ATF1<\/i>, <i>GREM2<\/i> AND <i>WNT10B<\/i> variants associated with tooth agenesis"],"prefix":"10.1111","volume":"24","author":[{"given":"Meredith","family":"Williams","sequence":"first","affiliation":[{"name":"Department of Orthodontics University of Texas Health Science Center School of Dentistry Houston 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