{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T09:59:22Z","timestamp":1774519162036,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,4,18]],"date-time":"2017-04-18T00:00:00Z","timestamp":1492473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["a Grant\u2010in\u2010Aid for Young Scientist (18790141)"],"award-info":[{"award-number":["a Grant\u2010in\u2010Aid for Young Scientist (18790141)"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Congenital Anomalies"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neural tube defects (NTD) are among the most common human congenital malformations, affecting 0.5\u20138.0\/1000 of live births. Human clinical trials have shown that periconceptional folate supplementation significantly decreases the occurrence of NTD in offspring. However, the mechanism by which folate acts on NTD remains largely unknown. Folate receptor (Folr) is one of the three membrane proteins that mediate cellular uptake of folates. Recent studies suggest that mouse <jats:italic>Folr1<\/jats:italic> (formerly referred to as <jats:italic>Fbp1<\/jats:italic>) is essential for neural tube closure. Therefore, we examined spatial and temporal expression patterns of <jats:italic>Folr1<\/jats:italic> in developing mouse embryos, showing a close association between <jats:italic>Folr1<\/jats:italic> and anterior neural tube closure. Transient transgenic analysis was performed using <jats:italic>lacZ<\/jats:italic> as a reporter; we identified a 1.1\u2010kb enhancer that directs <jats:italic>lacZ<\/jats:italic> expression in the neural tube and optic vesicle in a manner that is similar to endogenous <jats:italic>Folr1<\/jats:italic>. The 1.1\u2010kb enhancer sequences were highly conserved between humans and mice, suggesting that human <jats:italic>FOLR1<\/jats:italic> is associated with anterior neural tube closure in humans. Several experimental studies in mice and human epidemiological and genetics studies have suggested that folate receptor abnormalities are involved in a portion of human NTDs, although the solo defect of <jats:italic>FOLR1<\/jats:italic> did not cause NTD.<\/jats:p>","DOI":"10.1111\/cga.12218","type":"journal-article","created":{"date-parts":[[2017,2,28]],"date-time":"2017-02-28T07:24:53Z","timestamp":1488266693000},"page":"130-133","source":"Crossref","is-referenced-by-count":9,"title":["Folate receptors and neural tube closure"],"prefix":"10.1111","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0723-0960","authenticated-orcid":false,"given":"Hirotomo","family":"Saitsu","sequence":"first","affiliation":[{"name":"Department of Biochemistry Hamamatsu University School of Medicine  Higashi\u2010ku, Hamamatsu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,4,18]]},"reference":[{"key":"e_1_2_5_1_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.110.002766"},{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2008.08.002"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12327"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70110-8"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199212243272602"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2005.07.008"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23177"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20148"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3123"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20676"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-800223-0.00004-9"},{"key":"e_1_2_5_12_1","first-page":"68","article-title":"B 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