Abstract
BACKGROUND
Folate is an important B vitamin that is transported into cells by way of folate‐binding proteins and transporters. Folate‐binding protein‐2 nullizygous (Folbp2^−/−^) mice develop normally; however, we have found them to be more susceptible to the teratogenic effects of arsenate exposure than wild‐type control mice.
METHODS
In the current study, we wanted to extend our findings and test the hypothesis that Folbp2^−/−^ mice are more susceptible to the teratogenic effects of valproic acid (VPA), a commonly used antiepileptic drug that is known to induce neural tube defects (NTDs) in both humans and laboratory animals.
RESULTS
Folbp2^−/−^ mice had higher VPA‐induced frequencies of embryonic lethality and exencephaly than did the wild‐type control mice during folate supplementation and a control diet, respectively. All other differences in response between the two genotypes were short of reaching statistical significance. Folate supplementation of wild‐type, but not Folbp2^−/−^ dams reduced embryonic lethality of VPA‐treated wild‐type embryos compared to the folate‐deficient diet.
CONCLUSIONS
Unlike our previous findings with arsenate, enhanced susceptibility of Folbp2^−/−^ mice to in utero VPA exposure was demonstrated in some dietary folate regimens. Thus, our data indicate a relatively frail relationship between Folbp2 and VPA‐induced NTDs. Birth Defects Research (Part A) 67:000–000, 2003. © 2003 Wiley‐Liss, Inc.