FOLATE-DEFICIENCY ALONE DOES NOT PRODUCE NEURAL-TUBE DEFECTS IN MICE

The incidence of neural tube defects was studied in mouse embryos from dams fed an amino acid-based diet containing 45, 91, 136, 181, 227 or 453 nmol folic acid/kg diet (Experiment 1) or 227, 453, 566, 680, 906 , 1132, 1698 or 2266 nmol folic acid/kg diet (Experiment 2). Reproduct ive tracts were examined 12 d postcoitum and gross and microscopic exa mination of all embryos was performed. A single implantation was found at levels less-than-or-equal-to 181 nmol folic acid/kg diet. With one exception, bred mice fed 227 or 453 nmol folic acid/kg diet in Experi ment 1 had 100% resorptions. In Experiment 2, 100% of implantations in mice fed 227 nmol folic acid/kg diet and approximately 75% of implant ations in mice fed 453 or 566 nmol folic acid/kg diet resorbed. The 90 6 nmol folic acid/kg diet was sufficient for successful pregnancy. Mic e fed 227 nmol folic acid/kg diet in Experiment 2 weighed approximatel y 80% of mice fed higher levels of folic acid. Inadequate dietary foli c acid resulted in fewer and smaller embryos (which developed normally ). These results suggest that folate deficiency alone is insufficient to produce neural tube defects in Swiss-Webster mice. Because individu al micronutrients (e.g., folate) can be omitted from the amino acid-ba sed diet, the specific role of folic acid in neurulation can now be st udied systematically.