SCIENTISTS AT MONTREAL CHILDREN’S HOSPITAL DEVELOP AN ANIMAL MODEL IMPORTANT FOR THE STUDY OF BIRTH DEFECTS & CARDIOVASCULAR DISEASE


Montreal - March 1, 2001: A team of researchers led by Dr. Rima Rozen, a Canadian Genetic Diseases Network scientist based at McGill’s Montreal Children’s Hospital, has generated a mouse model with mutations of a gene which plays an important role in regulating inborn risks of neurological and vascular diseases. In the manuscript, published today in the journal Human Molecular Genetics, Dr. Rozen reports that mice with a knockout of the methylenetetrahydrofolate reductase gene (MTHFR) show a higher susceptibility to developmental retardation and cardiovascular disease.

The MTHFR gene is involved in the synthesis of an active form of the vitamin, folic acid, which regulates the level of an amino acid called homocysteine. An elevation of homocysteine in the blood can be caused by nutritional or genetic disruptions in homocysteine metabolism. The increased blood homocysteine is a risk factor for cardiovascular disease, among other problems. The most common genetic cause of elevated homocysteine is a mutation in the MTHFR gene. In earlier work, Dr. Rozen’s laboratory first cloned the MTHFR gene and identified the mutation which is associated with increased blood homocysteine and with an increased risk for vascular disease, birth defects, and pregnancy complications A role for the MTHFR gene in colon cancer and psychiatric disorders has also been proposed.

Approximately 10-15% of North Americans have two copies of the mutation in the MTHFR gene and may require higher levels of folate to prevent some of the associated disorders. Said Dr. Rozen "The availability of these mice will allow us to study the mechanisms that contribute to the diverse group of disorders affected by folate metabolism and, more importantly, to facilitate treatment or even prevention of disease." A CGDN core facility at McMaster University, headed by Dr. Michael Rudnicki, collaborated with Dr. Rozen in generating the knockout mice.

Dr. Michael Hayden, Scientific Director of the Canadian Genetic Diseases Network, commented "These new findings by Dr. Rozen and her team are an exciting advance in research into diseases related to inborn errors in metabolism as well as more common disorders. We look forward to results which will have an important impact on healthcare for all Canadians."