Inositol- and folate-resistant neural tube defects in mice lacking the epithelial-specific factor Gr
Author: ["Stephen B Ting","Tomasz Wilanowski","Alana Auden","Mark Hall","Anne K Voss","Tim Thomas","Vishwas Parekh","John M Cunningham","Stephen M Jane"]
Publication: Nature Medicine
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Abstract
The neural tube defects (NTDs) spina bifida and anencephaly are widely prevalent severe birth defects. The mouse mutant curly tail (ct/ct) has served as a model of NTDs for 50 years, even though the responsible genetic defect remained unrecognized. Here we show by gene targeting, mapping and genetic complementation studies that a mouse homolog of the Drosophila grainyhead (grh) gene, grainyhead-like-3 (Grhl3), is a compelling candidate for the gene underlying the curly tail phenotype. The NTDs in Grhl3-null mice are more severe than those in the curly tail strain, as the Grhl3 alleles in ct/ct mice are hypomorphic. Spina bifida in ct/ct mice is folate resistant, but its incidence can be markedly reduced by maternal inositol supplementation periconceptually. The NTDs in Grhl3−/− embryos are also folate resistant, but unlike those in ct/ct mice, they are resistant to inositol. These findings suggest that residual Grhl3 expression in ct/ct mice may be required for inositol rescue of folate-resistant NTDs.
Cite this article
Ting, S., Wilanowski, T., Auden, A. et al. Inositol- and folate-resistant neural tube defects in mice lacking the epithelial-specific factor Grhl-3. Nat Med 9, 1513–1519 (2003). https://doi.org/10.1038/nm961
