. "M Evidence from Animal Studies on the Etiology of Neural Tube Defects." Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: The National Academies Press, 1998.
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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline
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).
Copp AJ, Bernfield M. 1994. Etiology and pathogenesis of human neural tube defects: Insights from mouse models. Curr Opin Pediatr 6:624–631.
Essien FB. 1992. Maternal methionine supplementation promotes the remediation of axial defects in Axd mouse neural tube mutants. Teratology 45:205–212.
Finnell RH, Bennett GD, Karras SB, Mohl VK. 1988. Common hierachies of susceptibility to the induction of neural tube defects in mouse embryos by valproic acid and its 4-propyl-4-pentenoic acid metabolite. Teratology 38:313–320.
Greene ND, Copp AJ. 1997. Inositol prevents folate-resistant neural tube defects in the mouse. Nat Med 3:60–66.
Gruneberg H. 1954. Genetical studies on the skeleton of the mouse. 8. Curly tail. J Genet 52:52–67.
Heid MK, Bills ND, Hinrichs SH, Clifford AJ. 1992. Folate deficiency alone does not produce neural tube defects in mice. J Nutr 122:888–894.
Hendel J, Dam M, Gram L, Winkel P, Jorgensen I. 1984. The effects of carbamazepine and valproate on folate metabolism in man. Acta Neurol Scand 69:226–231.