Methionine but not folinic acid or vitamin B-12 alters the frequency of neural tube defects in Axd mutant mice

Abstract

The Axd (axial defects) mutation, which causes open neural tube defects (NTD) in 25-30% of d 14 mouse embryos of heterozygous (Axd/+) matings and curly tails (CT) in 31%, can be useful in studying neurovertebral morphogenesis. Current interest focuses on the role of methionine in neurulation, because supplementation of dams with this essential amino acid (70 mg/kg body wt) has been shown to reduce by 41% the incidence of NTD among embryos of Axd/+ x Axd/+ crosses when administered on d 8 and 9 of pregnancy. The present experiments were undertaken to determine whether supplementation of dams with a higher dose of methionine could effect a greater level of remediation. At a dose of 180 mg/kg body wt, the amino acid produced a reduction in NTD of 47%, similar to that produced at 70 mg/kg body wt. Supplementation of dams of reciprocal matings of Axd/+ x BALB/cByJ or CF-1 mice allowed assessment of the effects of methionine in heterozygous embryos, which exhibit CT. The amino acid had no effect on Axd/+ embryos from the BALB crosses, but the frequency of CT declined significantly among embryos of the CF-1 outcrosses. Maternal supplements of folinic acid (33 mg/kg) or vitamin B-12 (330 mg/kg) did not alter the incidence of NTD or CT among Axd embryos. No difference in methionine concentration was detected in the serum of Axd/+ and +/+ dams.