Valproate-induced neural tube defects in folate-binding protein-2 (Folbp2) knockout mice.
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.
Spiegelstein
Ofer
O
Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, Texas, USA. ofer.spiegelstein@teva.co.il
Merriweather
Michelle Y
MY
Wicker
Ned J
NJ
Finnell
Richard H
RH
D000014:Abnormalities, Drug-Induced; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000633:toxicity*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D020964:Embryo Loss / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009436:Neural Tube Defects / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D011247:Pregnancy / Q000097:blood; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D014635:Valproic Acid / Q000008:administration & dosage / Q000633:toxicity*
D000927:Anticonvulsants; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D014635:Valproic Acid; D005492:Folic Acid