Subtle decreases in DNA methylation and gene expression at the mouse Igf2 locus following prenatal alcohol exposure: effects of a methyl-supplemented diet.
Subtle decreases in DNA methylation and gene expression at the mouse Igf2 locus following prenatal alcohol exposure: effects of a methyl-supplemented diet.
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产前酒精暴露后小鼠 Igf2 基因座 DNA 甲基化和基因表达略有下降：甲基补充饮食的影响。
DOI：
10.1016/j.alcohol.2010.07.006
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发表时间：
2011-02
期刊：
影响因子：
2.3
通讯作者：
Cooney, Craig A.
中科院分区：
文献类型：
--
作者：
Downing, Chris;Johnson, Thomas E.;Larson, Colin;Leakey, Tatiana I.;Siegfried, Rachel N.;Rafferty, Tonya M.;Cooney, Craig A.
C57 BL/6 J（B6）小鼠在产前酒精暴露后易发生宫内生长迟缓和许多形态畸形，而DBA/2 J（D2）小鼠相对抵抗。我们以前已经表明，基因组印迹可能发挥作用，在B6和D2之间的差异敏感性。介导基因组印记的最佳表征机制是差异DNA甲基化。在本研究中，我们研究了DNA甲基化和基因表达，在胚胎和胎盘组织中，在小鼠Igf 2基因座在子宫内乙醇暴露。我们还研究了添加甲基的饮食对甲基化和乙醇致畸作用的影响。在易感B6小鼠的胚胎中，我们发现Igf 2基因座的一个差异甲基化区域的四个CpG位点的DNA甲基化略有下降;四个位点中只有一个显示出统计学显著性下降。我们没有观察到胎盘中甲基化的显著降低。所有Igf 2转录物显示约1.5倍减少后，宫内酒精暴露。在怀孕前和整个怀孕期间将母鼠置于补充甲基的饮食中，使甲基化恢复到对照水平。甲基补充剂还导致产前死亡率降低，产前生长更快，手指畸形减少;它大大减少了脊椎畸形。因此，虽然产前酒精对Igf 2基因座的DNA甲基化只有很小的影响，但将母鼠置于甲基补充饮食中部分改善了乙醇致畸作用。
C57BL/6J (B6) mice are susceptible to in utero growth retardation and a number of morphological malformations following prenatal alcohol exposure, while DBA/2J (D2) mice are relatively resistant. We have previously shown that genomic imprinting may play a role in differential sensitivity between B6 and D2. The best characterized mechanism mediating genomic imprinting is differential DNA methylation. In the present study we examined DNA methylation and gene expression, in both embryonic and placental tissue, at the mouse Igf2 locus following in utero ethanol exposure. We also examined the effects of a methyl-supplemented diet on methylation and ethanol teratogenesis. In embryos from susceptible B6 mice, we found small decreases in DNA methylation at four CpG sites in one of the differentially methylated regions of the Igf2 locus; only one of the four sites showed a statistically significant decrease. We observed no significant decreases in methylation in placentae. All Igf2 transcripts showed approximately 1.5 fold decreases following intrauterine alcohol exposure. Placing dams on a methyl-supplemented diet before pregnancy and throughout gestation brought methylation back up to control levels. Methyl-supplementation also resulted in lower prenatal mortality, greater prenatal growth, and decreased digit malformations; it dramatically reduced vertebral malformations. Thus, while prenatal alcohol had only small effects on DNA methylation at the Igf2 locus, placing dams on a methyl-supplemented diet partially ameliorated ethanol teratogenesis.
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影响因子：
2.6
作者：
Downing, C;Gilliam, D
通讯作者：
Gilliam, D
影响因子：
3.3
作者：
Boensch, D.;Lenz, B.;Bleich, S.
通讯作者：
Bleich, S.
影响因子：
5.1
作者：
CHRISTOFFEL, KK;SALAFSKY, I
通讯作者：
SALAFSKY, I
DOI：
10.1111/j.1530-0277.2006.00107.x
发表时间：
2006-06-01
期刊：
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
影响因子：
--
作者：
Dannenberg, Luke O.;Chen, Hui-Ju;Edenberg, Howard J.
通讯作者：
Edenberg, Howard J.
DOI：
10.1016/j.molbrainres.2003.10.025
发表时间：
2004-02-05
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Ravindran, CRM;Ticku, MK
通讯作者：
Ticku, MK