Does dietary folic acid supplementation in mouse NTD models affect neural tube development or gamete preference at fertilization?
Does dietary folic acid supplementation in mouse NTD models affect neural tube development or gamete preference at fertilization?
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DOI：
10.1186/s12863-014-0091-x
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发表时间：
2014-08-27
期刊：
影响因子：
2.9
通讯作者：
Nadeau JH
中科院分区：
文献类型：
--
作者：
Nakouzi GA;Nadeau JH
神经管缺陷（NTD）是人类第二大常见的出生缺陷。膳食叶酸（FA）补充剂有效和安全地降低了这些往往使人衰弱的先天性异常的发生率。FA在叶酸和同型半胱氨酸代谢中起着确定的作用，但其抑制NTD发生的方式尚不清楚。此外，许多情况下仍然抵抗叶酸补充剂的有益作用。为了更好地了解FA对NTD发挥作用的分子，生物化学和发育机制，需要具有明确遗传基础和已知对膳食补充剂反应的表征小鼠模型。我们检查了FA补充（5倍于对照饮食水平）对Apob tm1Unc和Vangl2 Lp小鼠（以下分别称为Apob和Lp）的NTD和椎骨表型的影响。补充FA的饮食没有降低Apob或Lp突变纯合子或Lp突变杂合子中的环尾表型中NTD的发生率或严重程度，表明具有这些突变等位基因的小鼠对FA补充具有抗性。补充叶酸也没有影响吸收率或窝仔的大小，而是使胚胎基因型分布偏向野生型等位基因。几种NTD模型也报告了类似的基因型偏倚，但被解释为饮食诱导的NTD发生率和严重程度增加，导致胚胎致死率增加。缺乏吸收率和窝仔数的差异反对诱导胚胎致死。我们提出了另一种解释，即FA补充剂导致强烈倾斜的等位基因遗传，也许是从多胺代谢的干扰，有利于野生型配子的受精偏见。
Neural tube defects (NTDs) are the second most common birth defect in humans. Dietary folic acid (FA) supplementation effectively and safely reduces the incidence of these often debilitating congenital anomalies. FA plays an established role in folate and homocysteine metabolism, but the means by which it suppresses occurrence of NTDs is not understood. In addition, many cases remain resistant to the beneficial effects of folic acid supplementation. To better understand the molecular, biochemical and developmental mechanisms by which FA exerts its effect on NTDs, characterized mouse models are needed that have a defined genetic basis and known response to dietary supplementation. We examined the effect of FA supplementation, at 5-fold the level in the control diet, on the NTD and vertebral phenotypes in Apob tm1Unc and Vangl2 Lp mice, hereafter referred to as Apob and Lp respectively. The FA supplemented diet did not reduce the incidence or severity of NTDs in Apob or Lp mutant homozygotes or the loop-tail phenotype in Lp mutant heterozygotes, suggesting that mice with these mutant alleles are resistant to FA supplementation. Folic acid supplementation also did not affect the rate of resorptions or the size of litters, but instead skewed the embryonic genotype distribution in favor of wild-type alleles. Similar genotypic biases have been reported for several NTD models, but were interpreted as diet-induced increases in the incidence and severity of NTDs that led to increased embryonic lethality. Absence of differences in resorption rates and litter sizes argue against induced embryonic lethality. We suggest an alternative interpretation, namely that FA supplementation led to strongly skewed allelic inheritance, perhaps from disturbances in polyamine metabolism that biases fertilization in favor of wild-type gametes.
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影响因子：
3.5
作者：
Gray, Jason D.;Nakouzi, Ghunwa;Ross, M. Elizabeth
通讯作者：
Ross, M. Elizabeth
DOI：
10.1016/s1357-2725(01)00014-0
发表时间：
2001-05-01
影响因子：
4
作者：
Kilpeläinen, PT;Saarimies, J;Hietala, OA
通讯作者：
Hietala, OA
在小鼠表观遗传敏感等位基因上DNA甲基化的动态重编程。
影响因子：
4.5
作者：
Blewitt ME;Vickaryous NK;Paldi A;Koseki H;Whitelaw E
通讯作者：
Whitelaw E
DOI：
10.4161/cc.23199
发表时间：
2013-01-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Bauer MA;Carmona-Gutiérrez D;Ruckenstuhl C;Reisenbichler A;Megalou EV;Eisenberg T;Magnes C;Jungwirth H;Sinner FM;Pieber TR;Fröhlich KU;Kroemer G;Tavernarakis N;Madeo F
通讯作者：
Madeo F
DOI：
10.1016/0140-6736(91)90133-a
发表时间：
1991-07-20
期刊：
Lancet (London, England)
影响因子：
--
作者：
通讯作者：
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