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curly tail mouse model (Greene and Copp, 1997). If curly tail is a suitable mouse model of human NTD, markers of inositol status should be evaluated with regard to human NTDs.


Many teratogens produce NTDs in rodents; exencephaly is especially common. Examples include ethanol, retinoic acid, vitamin A, and valproate (Sulik and Sadler, 1993). The NTD phenotype depends on the timing of administration. Early administration (before closure of the anterior neural tube at mouse embryonic day 9) most often results in exencephaly whereas later administration yields posterior defects. Valproate-induced NTDs are strain specific in the mouse (Finnell et al., 1988), highlighting the importance of genetic predisposition in NTD etiology. Although some studies show an alteration in folate levels (Hendel et al., 1984) and a protective effect of coadministered folic acid in valproate-induced NTD (Trotz et al., 1987), the metabolic mechanism of valproate teratogenesis is unclear (Nau, 1994).

In humans, carbamazepine is a commonly used antiepileptic drug that has been reported to cause NTDs at a higher-than-normal rate (Rosa, 1991). The absolute risk estimated from 21 cohort studies is approximately 1 percent (Rosa, 1991).


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Greene ND, Copp AJ. 1997. Inositol prevents folate-resistant neural tube defects in the mouse. Nat Med 3:60–66.

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