Dietary folate, but not choline, modifies neural tube defect risk in Shmt1 knockout mice

被引:43
作者
Beaudin, Anna E. [1 ]
Abarinov, Elena V. [1 ]
Malysheva, Olga [1 ]
Perry, Cheryll A. [1 ]
Caudill, Marie [1 ]
Stover, Patrick J. [1 ]
机构
[1] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA
关键词
MOUSE EMBRYOS; MASS-SPECTROMETRY; METABOLISM; METHYLENETETRAHYDROFOLATE; BETAINE; PLASMA;
D O I
10.3945/ajcn.111.020305
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
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. Design: 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). Conclusion: Maternal folate deficiency alone is sufficient to induce NTDs in response to embryonic Shmt1 disruption. Am J Clin Nutr 2012;95:109-14.
引用
收藏
页码:109 / 114
页数:6
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