Impact of methylenetetrahydrofolate reductase deficiency and low dietary folate on the development of neural tube defects in Splotch mice
Impact of methylenetetrahydrofolate reductase deficiency and low dietary folate on the development of neural tube defects in Splotch mice
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DOI：
10.1002/bdra.20223
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发表时间：
2006-01-01
影响因子：
--
通讯作者：
Rozen, R
中科院分区：
文献类型：
--
作者：
Li, DQ;Pickell, L;Rozen, R
背景：神经管缺陷（NTDs）的病因是多因素的，包括环境和遗传因素。叶酸补充剂可以预防大多数NTDs，亚甲基四氢叶酸还原酶（MTHFR）多态性已被认为是一种遗传风险因素。叶酸影响NTD发展的机制尚不清楚。斑点（Sp）小鼠是一种具有良好特征的研究自发性NTDs的小鼠模型。为了评估叶酸代谢与Sp突变体在NTD发育过程中的潜在相互作用，我们研究了Sp和Mthfr突变的小鼠，以及Sp与低叶酸饮食之间的相互作用。方法：将野生型、单Mthfr +/-突变型、单Sp/+突变型和双突变型（Mthfr +/-、Sp/+）雌性小鼠与相同基因型的雄性小鼠交配。胚胎在妊娠日（GD） 13.5时检查NTDs。为了研究叶酸缺乏对Sp小鼠的影响，Sp/+雌性小鼠分别饲喂对照饮食（CD）、中度叶酸缺乏饮食（MFADD）和重度叶酸缺乏饮食（SFADD）。将它们与Sp/+雄性交配，并检查胚胎。结果：与单Sp突变体的胚胎相比，双突变体的胚胎中ntd的发生率和严重程度没有差异。来自Mthfr +/-坝的胚胎未表现出NTDs。缺乏叶酸的饮食不影响Sp/+小鼠胚胎中NTDs的发生率或严重程度。结论：我们没有观察到Sp和Mthfr突变之间的相互作用，也没有观察到Sp突变与低叶酸饮食之间的相互作用。
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.