Mechanistic insights into folate supplementation from Crooked tail and other NTD-prone mutant mice.
Despite two decades of research since Smithells and colleagues began exploring its benefits, the mechanisms through which folic acid supplementation supports neural tube closure and early embryonic development are still unclear. The greatest progress toward a molecular-genetic understanding of folate effects on neural tube defect (NTD) pathogenesis has come from animal models. The number of NTD-associated mouse mutants accumulated and studied over the past decade has illuminated the complexity of both genetic factors contributing to NTDs and also NTD-gene interactions with folate metabolism. This article discusses insights gained from mouse models into how folate supplementation impacts neurulation. A case is made for renewed efforts to systematically screen the folate responsiveness of the scores of NTD-associated mouse mutations now identified. Designed after Crooked tail, supplementation studies of additional mouse mutants could build the molecular network maps that will ultimately enable tailoring of therapeutic regimens to individual families.
Gray
Jason D
JD
Laboratory of Neurogenetics and Development, Weill Medical College of Cornell University, New York, NY, USA.
Ross
M Elizabeth
ME
D000818:Animals; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D020022:Genetic Predisposition to Disease; D053858:Metabolic Networks and Pathways / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D008954:Models, Biological; D009436:Neural Tube Defects / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D011247:Pregnancy; D013623:Tail / Q000002:abnormalities* / Q000378:metabolism
D005492:Folic Acid