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

Abstract

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 Mthfd1^gt/+ 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.