دورية أكاديمية

Gene Expression Changes in C57 BL/6 J and DBA/2 J Mice Following Prenatal Alcohol Exposure.

التفاصيل البيبلوغرافية
العنوان: Gene Expression Changes in C57 BL/6 J and DBA/2 J Mice Following Prenatal Alcohol Exposure.
المؤلفون: Downing, Chris1, Flink, Stephen2, Florez-McClure, Maria L.3, Johnson, Thomas E.3,4, Tabakoff, Boris2, Kechris, Katerina J.5
المصدر: Alcoholism: Clinical & Experimental Research. Sep2012, Vol. 36 Issue 9, p1519-1529. 11p.
مصطلحات موضوعية: *ANALYSIS of variance, *ANIMAL experimentation, *CELL physiology, *ETHANOL, *GENE expression, *MICE, *POLYMERASE chain reaction, *POLYSACCHARIDES, *RESEARCH funding, *STATISTICS, *DATA analysis, *DATA analysis software, *OLIGONUCLEOTIDE arrays, *DESCRIPTIVE statistics
مستخلص: 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 C57 BL/6J ( B6) and DBA/2 J ( 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 2 hours in the morning, producing 4 embryonic genotypes: true-bred B6 B6 and D2 D2, and reciprocal B6 D2 and D2 B6. On gestational day 9, dams were intubated with 5.8 g/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 m RNA 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 m RNA 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. [ABSTRACT FROM AUTHOR]
قاعدة البيانات: Academic Search Index