Gene Expression Changes in C57BL/6J and DBA/2J Mice Following Prenatal Alcohol Exposure
Gene Expression Changes in C57BL/6J and DBA/2J Mice Following Prenatal Alcohol Exposure
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DOI：
10.1111/j.1530-0277.2012.01757.x
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发表时间：
2012-09-01
影响因子：
3.2
通讯作者：
Kechris, Katerina J.
中科院分区：
文献类型：
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作者：
Downing, Chris;Flink, Stephen;Kechris, Katerina J.
研究背景：产前酒精暴露可导致胎儿酒精谱系障碍（FASD）。并不是所有在怀孕期间饮酒的妇女都有患有FASD的孩子，研究表明遗传因素可以在乙醇致畸作用中发挥作用。我们检测了产前酒精暴露后C57 BL/6 J（B6）和DBA/2 J（D2）小鼠胚胎和胎盘中的基因表达。B6胎儿在产前接触酒精后容易出现形态畸形，而D2胎儿则相对具有抵抗力。方法将B6和D2小鼠雌雄交配2 h，产生4种胚胎基因型：纯种B6 B6和D2 D2，以及正反交B6 D2和D2 B6。在妊娠第9天，母鼠用5.8g/kg乙醇、等热量的麦芽糖糊精插管或不插管。4小时后，处死母鼠，收获胚胎和胎盘。提取RNA，标记并杂交到Affyssin Mouse Genome 430 v2微阵列芯片。数据经过标准化、方差分析，并使用注释、可视化和集成发现数据库（大卫）测试基因本体分子功能和生物过程的富集。结果B6和D2中有几类基因表达差异，包括多糖结合和有丝分裂相关基因。产前酒精暴露改变了一部分基因的表达，包括参与甲基化、染色质重塑、蛋白质合成和mRNA剪接的基因。在暴露于麦芽糖的组织和未接受任何麦芽糖的组织之间，很少有基因差异表达，因此我们将这些组与乙醇进行比较。虽然我们观察到许多特定的表达变化B6产前酒精暴露后，没有特异性D2。产前酒精暴露后B6中上调或下调的基因类别包括参与mRNA剪接、转录和翻译的基因。结论：我们的研究确定了几类基因的表达改变后，产前酒精暴露，包括许多特定的B6，一个菌株乙醇致畸敏感。在D2中缺乏菌株特异性效应表明几乎没有赋予抗性的基因表达变化。未来的研究将开始分析表达变化的功能意义。
Background Prenatal alcohol exposure can result in fetal alcohol spectrum disorders (FASD). Not all women who consume alcohol during pregnancy have children with FASD and studies have shown that genetic factors can play a role in ethanol teratogenesis. We examined gene expression in embryos and placentae from C57BL/6J (B6) and DBA/2J (D2) mice following prenatal alcohol exposure. B6 fetuses are susceptible to morphological malformations following prenatal alcohol exposure while D2 are relatively resistant. Methods Male and female B6 and D2 mice were mated for 2hours in the morning, producing 4 embryonic genotypes: true-bred B6B6 and D2D2, and reciprocal B6D2 and D2B6. On gestational day 9, dams were intubated with 5.8g/kg ethanol, an isocaloric amount of maltose dextrin, or nothing. Four hours later, dams were sacrificed and embryos and placentae were harvested. RNA was extracted, labeled and hybridized to Affymetrix Mouse Genome 430 v2 microarray chips. Data were normalized, subjected to analysis of variance and tested for enrichment of gene ontology molecular function and biological process using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Results Several gene classes were differentially expressed in B6 and D2 regardless of treatment, including genes involved in polysaccharide binding and mitosis. Prenatal alcohol exposure altered expression of a subset of genes, including genes involved in methylation, chromatin remodeling, protein synthesis, and mRNA splicing. Very few genes were differentially expressed between maltose-exposed tissues and tissues that received nothing, so we combined these groups for comparisons with ethanol. While we observed many expression changes specific to B6 following prenatal alcohol exposure, none were specific for D2. Gene classes up- or down-regulated in B6 following prenatal alcohol exposure included genes involved in mRNA splicing, transcription, and translation. Conclusions Our study identified several classes of genes with altered expression following prenatal alcohol exposure, including many specific for B6, a strain susceptible to ethanol teratogenesis. Lack of strain specific effects in D2 suggests there are few gene expression changes that confer resistance. Future studies will begin to analyze functional significance of the expression changes.