Embryonic development of folate binding protein-1 (Folbp 1) knockout mice: Effects of the chemical form, dose, and timing of maternal folate supplementation
Embryonic development of folate binding protein-1 (Folbp 1) knockout mice: Effects of the chemical form, dose, and timing of maternal folate supplementation
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DOI：
10.1002/dvdy.20107
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发表时间：
2004-09-01
影响因子：
2.5
通讯作者：
Finnell, RH
中科院分区：
文献类型：
--
作者：
Spiegelstein, O;Mitchell, LE;Finnell, RH
叶酸结合蛋白-1 （Folbp1）失活会对小鼠胚胎发育产生不利影响，因为无合子胚胎（Folbp1(-/-)）在子宫内死亡。叶酸（n5 -甲酰基四氢叶酸）在妊娠前和妊娠期间给予叶酸缺乏的胚胎，可挽救大多数胚胎免于过早死亡；然而，一部分存活下来的胚胎会出现结构畸形，包括神经管缺陷。与l- n5 -甲酰基四氢叶酸（L-5F-THF）相比，我们研究了母体补充l- n5 -甲基四氢叶酸（L-5M-THF）是否对Folbp1（-/-）胎儿的胚胎发育具有更好的保护作用。我们还研究了在妊娠期间补充叶酸对发育中的Folbp1（-/-）胚胎最有利的关键时期。Folbp1（-/-）幼崽表现出一系列畸形，包括神经管、颅相、眼睛和腹壁。这些畸形的频率随着叶酸剂量的增加而降低，无论使用何种形式。与L-5F-THF相比，L-5M-THF没有提供额外的益处。尽管修复了Folbp1（-/-）胚胎的表型，但补充叶酸后并未观察到Folbp1（-/-）母体叶酸水平的显著升高。(C) 2004 Wiley-Liss, Inc。
Inactivation of folate binding protein-1 (Folbp1) adversely impacts murine embryonic development, as nullizygous embryos (Folbp1(-/-)) die in utero. Administration of folinic acid (N5-formyl-tetrahydrofolate) to Folbp1-deficient dams before and throughout gestation rescues the majority of embryos from premature death; however, a portion of surviving embryos develop structural malformations, including neural tube defects. We examined whether maternal supplementation with L-N5-methyl-tetrahydrofolate (L-5M-THF) has superior protective effects on embryonic development of Folbp1(-/-) fetuses compared with L-N5-formyl-tetrahydrofolate (L-5F-THF). We also examined the critical period during gestation when folate supplementation is most beneficial to the developing Folbp1(-/-) embryos. Folbp1(-/-) pups presented with a range of malformations involving the neural tube, craniofacies, eyes, and abdominal wall. The frequencies of these malformations decreased with increasing folate dose, regardless of the form used. There was no additional benefit provided by L-5M-THF compared with L-5F-THF. Despite rescuing the phenotype in Folbp1(-/-) embryos, no significant elevation of Folbp1(-/-) maternal folate levels was observed with supplementation. (C) 2004 Wiley-Liss, Inc.