Failure of homocysteine to induce neural tube defects in a mouse model.
BACKGROUND
Folate deficiencies have been associated with many adverse congenital abnormalities. It is not clear, however, whether these defects are due to a folate deficiency or to an increase in homocysteine. Homocysteine has been shown to be teratogenic in the chicken-embryo model and it has been suggested that homocysteine-induced defects are mediated by inhibiting the N-methyl-D-aspartate (NMDA) receptor on neural crest cells. The majority of the teratology studies have been carried out using the chicken embryo model. In an effort to develop a murine model of homocysteine-induced neural tube defects, several inbred mouse strains were treated with homocysteine or the NMDA inhibitor MK801 and the fetuses examined for any induced-NTD.


METHODS
Several in-bred mouse strains were administered homocysteine once on gestational day (GD) E8.5 or once daily on GD 6.5-10.5. Additionally, because homocysteine was been reported to mediate its effects through the NMDA receptor, the effect of MK801, an antagonist of this receptor, was also investigated.


RESULTS
Regardless of the mouse treatment time, homocysteine failed to induce neural tube defects in our in-bred mouse strains. Homocysteine also failed to increase the number of neural tube defects in the splotch strain, regardless of the genotype.


CONCLUSIONS
Irrespective of the mouse strain or treatment, homocysteine failed to induce neural tube defects in our mouse models, which is in contrast to what has been reported in the chicken embryo models.
Bennett
Gregory D
GD
Department of Genetics Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska 68198-5805, USA. gbennett@unmc.edu
Vanwaes
Janee
J
Moser
Kristine
K
Chaudoin
Tammy
T
Starr
Lois
L
Rosenquist
Thomas H
TH
D000818:Animals; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006711:Homocystine / Q000633:toxicity*; D051379:Mice / Q000002:abnormalities*; D008815:Mice, Inbred Strains; D009436:Neural Tube Defects / Q000139:chemically induced*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D006711:Homocystine; D016291:Dizocilpine Maleate