title: Dietary folate, but not choline, modifies neural tube defect risk in Shmt1 knockout mice.
abstract: BACKGROUND
  Low dietary choline intake has been proposed to increase the risk of neural tube defects (NTDs) in human populations. Mice with reduced Shmt1 expression exhibit a higher frequency of NTDs when placed on a folate- and choline-deficient diet and may represent a model of human NTDs. The individual contribution of dietary folate and choline deficiency to NTD incidence in this mouse model is not known.
  
  
  OBJECTIVE
  To dissociate the effects of dietary folate and choline deficiency on Shmt1-related NTD sensitivity, we determined NTD incidence in embryos from Shmt1-null dams fed diets deficient in either folate or choline.
  
  
  METHODS
  Shmt1(+/+) and Shmt1(-/-) dams were maintained on a standard AIN93G diet (Dyets), an AIN93G diet lacking folate (FD), or an AIN93G diet lacking choline (CD). Virgin Shmt1(+/+) and Shmt1(-/-) dams were crossed with Shmt1(+/-) males, and embryos were examined for the presence of NTDs at embryonic day (E) 11.5 or E12.5.
  
  
  RESULTS
  Exencephaly was observed only in Shmt1(-/-) embryos isolated from dams maintained on the FD diet (P = 0.004). Approximately 33% of Shmt1(-/-)embryos (n = 18) isolated from dams maintained on the FD diet exhibited exencephaly. NTDs were not observed in any embryos isolated from dams maintained on the CD (n = 100) or control (n = 152) diets or in any Shmt1(+/+) (n = 78) or Shmt1(+/-) embryos (n = 182).
  
  
  CONCLUSIONS
  Maternal folate deficiency alone is sufficient to induce NTDs in response to embryonic Shmt1 disruption.
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Beaudin
authors.forename: Elena V
authors.initials: EV
authors.lastname: Abarinov
authors.forename: Olga
authors.initials: O
authors.lastname: Malysheva
authors.forename: Cheryll A
authors.initials: CA
authors.lastname: Perry
authors.forename: Marie
authors.initials: M
authors.lastname: Caudill
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Stover
mesh_terms: D000818:Animals; D002794:Choline / Q000494:pharmacology*; D002796:Choline Deficiency / Q000150:complications*; D004032:Diet; D004195:Disease Models, Animal; D002149:Energy Intake; D005492:Folic Acid / Q000494:pharmacology*; D005494:Folic Acid Deficiency / Q000150:complications*; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009436:Neural Tube Defects / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control; D012307:Risk Factors
chemical_list: D005492:Folic Acid; D012696:Glycine Hydroxymethyltransferase; C559685:Shmt1 protein, mouse; D002794:Choline