{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:09:26Z","timestamp":1791144566683,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,10,12]],"date-time":"2009-10-12T00:00:00Z","timestamp":1255305600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2010,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>BACKGROUND<\/jats:bold>: Suboptimal maternal folate status is considered a risk factor for neural tube defects (NTDs). However, the relationship between dietary folate status and risk of NTDs appears complex, as experimentally induced folate deficiency is insufficient to cause NTDs in nonmutant mice. In contrast, folate deficiency can exacerbate the effect of an NTD\u2010causing mutation, as in<jats:italic>splotch<\/jats:italic>mice. The purpose of the present study was to determine whether folate deficiency can induce NTDs in mice with a permissive genetic background which do not normally exhibit defects.<jats:bold>METHODS<\/jats:bold>: Folate deficiency was induced in<jats:italic>curly tail<\/jats:italic>and genetically matched wild\u2010type mice, and we analyzed the effect on maternal folate status, embryonic growth and development, and frequency of NTDs.<jats:bold>RESULTS<\/jats:bold>: Folate\u2010deficient diets resulted in reduced maternal blood folate, elevated homocysteine, and a diminished embryonic folate content. Folate deficiency had a deleterious effect on reproductive success, resulting in smaller litter sizes and an increased rate of resorption. Notably, folate deficiency caused a similar\u2010sized, statistically significant increase in the frequency of cranial NTDs among both<jats:italic>curly tail<\/jats:italic>(<jats:italic>Grhl3<\/jats:italic>mutant) embryos and background\u2010matched embryos that are wild type for<jats:italic>Grhl3<\/jats:italic>. The latter do not exhibit NTDs under normal dietary conditions. Maternal supplementation with<jats:italic>myo<\/jats:italic>\u2010inositol reduced the incidence of NTDs in the folate\u2010deficient wild\u2010type strain.<jats:bold>CONCLUSIONS<\/jats:bold>: Dietary folate deficiency can induce cranial NTDs in nonmutant mice with a permissive genetic background, a situation that likely parallels gene\u2010nutrient interactions in human NTDs. Our findings suggest that inositol supplementation may ameliorate NTDs resulting from insufficient dietary folate. 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