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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #152468
Title: THE CURLY-TAIL (CT) MOUSE, AN ANIMAL MODEL OF NEURAL TUBE DEFECTS, DISPLAYS ALTERED HOMOCYSTEINE METABOLISM WITHOUT FOLATE RESPONSIVENESS OR A DEFECT IN MTHFR

Author
item TRAN, PAMELA - MCGILL U, MONTREAL, CA
item HIOU-TIM, FRANCOIS - MCGILL U, MONTREAL, CA
item FROSST, PHYLLIS - MCGILL U, MONTREAL, CA
item LUSSIER-CACAN, SUZANNE - INSTITUT DE RECHERCHES CL
item BAGLEY, PAMELA - HNRCA
item SELHUB, JACOB - HNRCA
item BOTTIGLIERI, TEODORO - BAYLOR U MED CTR, DALLAS,
item ROZEN, RIMA - MCGILL U, MONTREAL, CA

Submitted to: Molecular Genetics and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/12/2002
Publication Date: 8/1/2002
Citation: TRAN, P., HIOU-TIM, F., FROSST, P., LUSSIER-CACAN, S., BAGLEY, P., SELHUB, J., BOTTIGLIERI, T., ROZEN, R. THE CURLY-TAIL (CT) MOUSE, AN ANIMAL MODEL OF NEURAL TUBE DEFECTS, DISPLAYS ALTERED HOMOCYSTEINE METABOLISM WITHOUT FOLATE RESPONSIVENESS OR A DEFECT IN MTHFR. MOLECULAR GENETICS AND METABOLISM. 2002;76:297-304.

Interpretive Summary: Natural tube defects or NTD is a birth defects which is caused by the inability of the closure of the neural tube that forms the brain and the spinal cord, during gestation. Although we know that NTD can be prevented by taking folic acid before pregnancy, we still do not know how folic acid accomplishes this. The curly tail mouse has been used extensively because the curly tail serves as a model of NTD. This study failed to show relationship with folic acid in this model.

Technical Abstract: Maternal mild hyperhomocysteinemia is associated with increased risk for bearing children with neural tube defects (NTD). Folate intake corrects hyperhomocysteinemia and prevents up to 70% of NTD. The curly-tail (ct) mouse, an animal model for NTD, has been suggested to display features that closely resemble the human defect. We therefore investigated folate metabolism in ct mice. On control and folate-/choline-deficient diets, ct mice exhibited higher plasma homocysteine levels than control C57Bl/6 mice. This increase was associated with increased liver S-Adenosylhomocysteine and decreased S-adenosylmethionine:S-adenosylhomocysteine (SAM/SAH) ratios. Since the ct locus maps in close proximity to the gene for methylenetetrahydrofolate reductase (Mthfr), a modifier of homocysteine levels in man, we also assayed Mthfr activity and sequenced the 5(') regulatory region; these experiments suggested that Mthfr is not defective in the ct strain. Finally, we examined the influence of dietary folate on NTD incidence in the ct strain, but did not identify significant differences among the four diets used in the study. Our work suggests that altered homocysteine metabolism may contribute to the pathogenetic mechanism of the ct defect, but, unlike human NTD, nutritional or genetic deficiencies in folate metabolism do not appear to play a significant direct role.