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Defects in <jats:italic>splotch<\/jats:italic> mice result from mutations in <jats:italic>Pax3<\/jats:italic>, and some human NTDs may also result from mutations in the human <jats:italic>PAX3<\/jats:italic> gene. <jats:italic>Pax3<\/jats:italic> encodes a transcription factor whose function may influence expression of multiple downstream genes associated with a variety of cellular properties (including apoptosis, adhesion, proliferation, and differentiation), that could be important for neural tube closure. The frequency of NTDs varies between mutant alleles and is also influenced by genetic background and environmental factors. Notably, <jats:italic>splotch<\/jats:italic> provides a model for folic acid\u2013preventable NTDs, and conversely, dietary folate deficiency exacerbates NTDs. Understanding the molecular and cellular basis of <jats:italic>splotch<\/jats:italic> NTDs, as well as the mechanisms by which the frequency of defects is influenced by genetic and environmental factors (such as sub\u2010optimal folate status), may provide insight into the causation of these severe congenital malformations in humans. Birth Defects Research (Part A) 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/bdra.20539","type":"journal-article","created":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T19:27:33Z","timestamp":1233343653000},"page":"322-330","source":"Crossref","is-referenced-by-count":45,"title":["Understanding the causes and prevention of neural tube defects: Insights from the <i>splotch<\/i> mouse model"],"prefix":"10.1002","volume":"85","author":[{"given":"Nicholas D.E.","family":"Greene","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Massa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew 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