Folate Metabolism In The ICR Mouse, Behavioral and Genetic Analyses

Folate supplementation during pregnancy can prevent neural tube defects in the developing fetus, but recent analyses suggest a link between excess perinatal folate and autism spectrum disorders. We have been studying the effects of excess folate in the ICR mouse strain, looking at effects on organogenesis and postnatal behavior. In human populations it is known that different ethnic groups vary in their response to supplemental folate and this has been linked to the MTHFR, DHFR and RFC1 genes, which play roles in folate metabolism and the one-carbon cycle.  Given that we are working with an outbred mouse strain, we are asking if the ICR strain harbors variants in genes central to folate uptake and metabolism that may be contributing to the variation we have observed within treatment groups and families. Sequence analysis of the MTHFR gene,, a large 11 exon gene with an mRNA length of 6,085 bases, is on going. Initial coded data from the behavioral project came from the T-maze cognitive testing of past and current pups. The behaviors observed in the t-maze tests were highly variable but even with just this simplest of sorting analysis, it is clear that significant differences exist between treatment groups from the same developmental period.  We are also seeing significant differences within treatment groups by comparing animals treated at different developmental periods. Data from the sequencing project will be combined with data from the behavioral studies to determine if the genotype of the animal influences its’ response to perinatal folate supplementation.