Effects of Mthfd1 Gene on Mouse Behavior

Abstract

Methylenetetrahydrofolate dehydrogenase 1 (Mthfd1) gene encodes the trifunctional C1 tetrahydrofolate (C1THF) enzyme that plays an important role in the folate-mediated one-carbon metabolism. A polymorphism of this gene (1958G>A; rs2236225) has been associated in humans with neural tube defects and with neuropsychiatric disorders such as bipolar disorder, depression, and schizophrenia. This gene has been shown to be essential in mice and moderate deficiency has been associated with impaired fetal growth. To understand the effects of moderate C1THF deficiency on cognition and behavior, we are running a battery of behavioral tests at adulthood on Mthfd1gt/+ and Mthfd1+/+ mice. We are assessing both male and female mice for locomotor activity (open field), sensorimotor function (rotarod), anxiety (open field and light-dark box), novel object and social investigation, and spatial memory (Morris Water maze). Our initial results show no difference between the heterozygous mice and wild type litter mates on locomotor activity and anxiety, as assessed in the open field. We also did not observe a difference in the novel object investigation. These findings and the results that will be obtained when the tests will be complete, will give us a picture of the role of Mthfd1 gene on behavior. This research is funded from Nutrition Research Institute, UNC Chapel Hill.