Investigation of the effects of folate deficiency on embryonic development through the establishment of a folate deficient mouse model.
BACKGROUND
Folic acid (FA) has been shown to reduce the incidence of neural tube, craniofacial, and cardiovascular defects and low birth weight. The mechanism(s) by which the vitamin is effective, however, has not been determined. Therefore, a folic acid deficient mouse model was developed.


METHODS
To create a folic acid deficiency, ICR female mice were placed on a diet containing no FA and including 1% succinyl sulfathiazole (SS) for 4 weeks before mating. Control mice were fed diets with either: 1) FA and 1% SS [+SS only diet]; 2) FA [normal diet]; or 3) a breeding diet. Dams and fetuses were examined during various days of gestation.


RESULTS
Blood analysis showed that by gestational day 18, plasma folate concentrations in the -FA+SS fed dams decreased to 1.13 ng/ml, a concentration approximately 3% of that in breeding diet fed dams (33.24 ng/ml) and 8% of that in +SS only/normal fed dams (13.59 ng/ml). RBC folate levels showed a similar decrease, whereas homocysteine concentrations increased. Reproductive outcome in the -FA+SS fed dams was poor with increased fetal deaths, decreased fetal weight, and delays in palate and heart development.


CONCLUSIONS
Female mice fed a folic acid deficient diet and 1% succinyl sulfathiazole exhibited many of the characteristics common to human folic acid deficiency, including decreased plasma and RBC folate, increased plasma homocysteine, and poor reproductive outcomes. Thus, an excellent model has been created to investigate the mechanism(s) underlying the origin of birth defects related to folic acid deficiency.
Burgoon
Jennifer M
JM
Department of Cell and Developmental Biology, School of Medicine, University of North Carolina, Chapel Hill 27599-7090, USA.
Selhub
Jacob
J
Nadeau
Marie
M
Sadler
T W
TW
D000818:Animals; D001835:Body Weight; D002972:Cleft Palate; D004195:Disease Models, Animal; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000378:metabolism; D005494:Folic Acid Deficiency / Q000196:embryology*; D006330:Heart Defects, Congenital; D006710:Homocysteine / Q000097:blood / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009436:Neural Tube Defects; D011247:Pregnancy
D006710:Homocysteine; D005492:Folic Acid