Grant: Operating Grant

Folic acid is an important B vitamin which is involved in several different common disorders, including neural tube defects (such as spina bifida), vascular disease and cancer. Other less well-characterized associations with folate deficiency include pregnancy complications and neuropsychiatric disorders. We had isolated an important gene in folate metabolism (MTHFR) and identified a mutation that increases risk for having a child with spina bifida and for developing vascular disease. In contrast, we found that this mutation decreased risk for colon cancer under certain conditions. Approximately 10 - 15% of North Americans and Europeans may be implicated, particularly if their folate intake is low. We have generated mice which serve as an animal model for MTHFR deficiency in human populations. In this application, we shall determine whether pregnant mice that carry this mutation, in combination with nutritional deficiencies, exhibit pregnancy complications and birth defects in their offspring. We shall examine the impact of this mutation on brain development and behaviour and determine whether there is a different response to infection in mice with MTHFR deficiency. Since food is fortified with folate in Canada and the US, we shall repeat some of the afore-mentioned studies in mice fed very high levels of folic acid. Our work will have an impact on prevention and modulation of common diseases that are influenced by genetic and nutritional disturbances in folate metabolism.