Studies on mice have indicated that female embryos are more susceptible to NTDs than males in some, but not all, genetic models.34 For example, there is a higher rate of cranial NTDs in mice carrying mutations in Trp53,6 Pax3, or Nf135 but not Gldc. 36 Sex differences in NTD susceptibility in Trp53 null mice may result from the presence of two X chromosomes and independent of the Y chromosome.6 Given the association between abnormal one-carbon metabolism or impaired methylation and NTDs, it has been hypothesised that the higher rate of cranial NTDs in females may be an epigenetic phenomenon. This evidence concerns the gene PAX3 and neural tube defect.