The cause of neural tube defects: some experiments and a hypothesis.
The mouse mutant curly-tail is an animal model for human neural tube defects (NTD). Around 60% spontaneously have NTD. It has been found that maternal administration of hydroxyurea, mitomycin C, or 5-fluorouracil on day 9 of pregnancy, that is, when the fetal neural tube is in the final stages of closure, leads to a significant reduction in the proportion of NTD (to 15 to 20%) in the offspring, while total litter size is unaffected. All these substances are inhibitors of DNA synthesis, yet are apparently beneficial to subjects predisposed to NTD. As a consequence, it is suggested that the underlying mechanism causing NTD in the mice, and also in man, is a basic metabolic defect in DNA synthesis which affects cell replication and results in abnormal morphogenesis of the neuraxis.
D000818:Animals; D004247:DNA / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D005865:Gestational Age; D006918:Hydroxyurea / Q000494:pharmacology; D051379:Mice; D008817:Mice, Mutant Strains / Q000196:embryology*; D008937:Mitomycins / Q000494:pharmacology; D009436:Neural Tube Defects / Q000209:etiology*; D011247:Pregnancy
D008937:Mitomycins; D004247:DNA; D005472:Fluorouracil; D006918:Hydroxyurea