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 Medjournal_title
Nature medicineauthors
Ting SB,Wilanowski T,Auden A,Hall M,Voss AK,Thomas T,Parekh V,Cunningham JM,Jane SMdoi
10.1038/nm961keywords:
subject
Has Abstractpub_date
2003-12-01 00:00:00pages
1513-9issue
12eissn
1078-8956issn
1546-170Xpii
nm961journal_volume
9pub_type
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