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

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.

journal_name

Nat Med

journal_title

Nature medicine

authors

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

doi

10.1038/nm961

keywords:

subject

Has Abstract

pub_date

2003-12-01 00:00:00

pages

1513-9

issue

12

eissn

1078-8956

issn

1546-170X

pii

nm961

journal_volume

9

pub_type

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