With all the uncertainty of COVID-19, we hope you are safe and in good health. Ozgene is still here to meet your research needs.

Inositol- and folate-resistant neural tube defects in mice lacking the epithelial-specific factor Grhl-3

 Back to publications

2003

Nat Med. 2003 Dec;9(12):1513-9. Epub 2003 No

Inositol- and folate-resistant neural tube defects in mice lacking the epithelial-specific factor Grhl-3

Auden, A;Cunningham, JM;Hall, M;Jane, SM.;Parekh, V;Thomas, T;Ting, SB;Voss, AK;Wilanowski, T

Royal Melbourne Hospital Post Office, Grattan Street, Parkville, Victoria, Australia 3050.

Service type: Knock-in mice

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.

View Publication