Deletion of one allele of Mthfd1 (methylenetetrahydrofolate dehydrogenase 1) impairs learning in mice

Behav Brain Res. 2017 Aug 14:332:71-74. doi: 10.1016/j.bbr.2017.05.051. Epub 2017 May 27.


The MTHFD1 gene encodes for methylenetetrahydrofolate dehydrogenase 1, an enzyme that has an important role in folate-mediated one-carbon metabolism. In people, a single nucleotide polymorphism of this gene (1958G>A; rs2236225) is associated with increased risk for bipolar disorder and schizophrenia, neural tube and other birth defects. Mice homozygous for a loss of Mthfd1 via a gene-trap mutation are not viable, and heterozygotes, though they appear healthy, have metabolic imbalances in the folate- and choline-mediated 1-carbon metabolic pathways. In this study, we evaluated cognitive function in Mthfd1gt/+ male and female mice using a behavioral battery composed of eight different tests. We found that these mice display impaired cue-conditioned learning, while other behaviors remain intact.

Keywords: Learning; Male and female mice; Mouse behavior; Mthfd1.

MeSH terms

  • Animals
  • Body Weight
  • Cognition / physiology
  • Female
  • Formate-Tetrahydrofolate Ligase / deficiency*
  • Formate-Tetrahydrofolate Ligase / genetics
  • Learning Disabilities / enzymology*
  • Male
  • Methenyltetrahydrofolate Cyclohydrolase / deficiency*
  • Methenyltetrahydrofolate Cyclohydrolase / genetics
  • Methylenetetrahydrofolate Dehydrogenase (NADP) / deficiency*
  • Methylenetetrahydrofolate Dehydrogenase (NADP) / genetics
  • Mice, Transgenic
  • Multifunctional Enzymes / deficiency*
  • Multifunctional Enzymes / genetics
  • Neuropsychological Tests
  • Phenotype


  • Mthfd1 protein, mouse
  • Multifunctional Enzymes
  • Methylenetetrahydrofolate Dehydrogenase (NADP)
  • Methenyltetrahydrofolate Cyclohydrolase
  • Formate-Tetrahydrofolate Ligase