title: Impact of methylenetetrahydrofolate reductase deficiency and low dietary folate on the development of neural tube defects in splotch mice.
abstract: BACKGROUND
  The etiology of neural tube defects (NTDs) is multifactorial, with environmental and genetic determinants. Folate supplementation prevents the majority of NTDs, and a polymorphism in methylenetetrahydrofolate reductase (MTHFR) has become recognized as a genetic risk factor. The mechanisms by which folate affects NTD development are unclear. The Splotch (Sp) mouse is a well-characterized mouse model for studying spontaneous NTDs. To assess the potential interaction between folate metabolism and the Sp mutant in NTD development, we studied mice with both Sp and Mthfr mutations, as well as the interaction between Sp and low dietary folate.
  
  
  METHODS
  Wild-type, single Mthfr+/-mutant, single Sp/+mutant, and double mutant (Mthfr+/-, Sp/+) female mice were mated with males of the same genotype. Embryos were examined for NTDs on gestational day (GD) 13.5. To investigate the effects of folate deficiency on Sp mice, Sp/+female mice were fed a control diet (CD), a moderately folic acid-deficient diet (MFADD), or a severely folic acid-deficient diet (SFADD). They were mated with Sp/+males and the embryos were examined.
  
  
  RESULTS
  There were no differences in the incidence or severity of NTDs in embryos from double-mutant mating pairs compared to those from single Sp mutants. Embryos from Mthfr+/-dams did not exhibit NTDs. Diets deficient in folate did not influence the incidence or severity of NTDs in embryos from Sp/+mice.
  
  
  CONCLUSIONS
  We did not observe an interaction between Sp and Mthfr mutations, or between the Sp mutation and low dietary folate, in NTD development in Splotch mice.
authors.affiliation: Department of Human Genetics, McGill University-Montreal Children's Hospital Research Institute, Montreal, Canada.
authors.forename: Deqiang
authors.initials: D
authors.lastname: Li
authors.forename: Laura
authors.initials: L
authors.lastname: Pickell
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Rima
authors.initials: R
authors.lastname: Rozen
mesh_terms: D000818:Animals; D005260:Female; D005494:Folic Acid Deficiency / Q000150:complications*; D005865:Gestational Age; D006579:Heterozygote; D006710:Homocysteine / Q000097:blood; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D009436:Neural Tube Defects / Q000235:genetics* / Q000517:prevention & control; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D011247:Pregnancy
chemical_list: D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D006710:Homocysteine; C068686:Pax3 protein, mouse; D042965:Methylenetetrahydrofolate Reductase (NADPH2)