Valproate-induced neural tube defects in folate-binding protein-2 (Folbp2) knockout mice.

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.

• Authors: Ofer Spiegelstein, Michelle Y Merriweather, Ned J Wicker, Richard H Finnell
• Journal: Birth defects research. Part A, Clinical and molecular teratology (Birth Defects Res A Clin Mol Teratol) Vol. 67 Issue 12 Pg. 974-8 (Dec 2003) ISSN: 1542-0752 [Print] United States
• PMID: 14745917 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2003 Wiley-Liss, Inc.

Chemical References

• Anticonvulsants
• Carrier Proteins
• Folate Receptors, GPI-Anchored
• Receptors, Cell Surface
• Valproic Acid
• Folic Acid

Topics

• Abnormalities, Drug-Induced
• Animals
• Anticonvulsants (administration & dosage, toxicity)
• Carrier Proteins (genetics, metabolism)
• Diet
• Disease Models, Animal
• Embryo Loss (chemically induced, pathology, prevention & control)
• Female
• Folate Receptors, GPI-Anchored
• Folic Acid (administration & dosage, blood, therapeutic use)
• Injections, Intraperitoneal
• Male
• Mice
• Mice, Inbred Strains
• Mice, Knockout
• Neural Tube Defects (chemically induced, pathology, prevention & control)
• Pregnancy (blood)
• Receptors, Cell Surface (genetics, metabolism)
• Valproic Acid (administration & dosage, toxicity)