Identity and neuroanatomical localization of messenger RNAs that change expression in the neural tube of mouse embryos within 1 h after ethanol exposure.

Changes in the expression of various species of messenger RNA (mRNA) are likely to be one of the initial responses of an embryo to in utero ethanol exposure. However, the identity and range of the initial species of mRNAs that change expression in an embryo after acute prenatal ethanol exposure are unknown. mRNA was isolated from embryos treated on embryonic day 9.5 and examined 1 h after treatment. Ethanol-exposed embryos were compared to similarly treated maltose/dextrin and no injection control embryos. Subtractive hybridization was used to find the species of mRNAs. The identity of the differentially expressed mRNAs was ascertained using standard sequencing techniques while in situ hybridization defined the anatomical localization of each message. Four messages from ethanol-treated embryos were differentially expressed. One message has no homology to any known gene in GenBank while three messages are homologous to known genes: the transmembrane molecule mh19, the heterologous ribonuclear protein hnRNP A3, and the mitochondrial enzyme AK2. One message (the novel gene) was turned on, while mh19, AK2 and hnRNP A3 were up-regulated in ethanol-exposed embryos. All messages were expressed in the developing neural tube of the ethanol-exposed embryos, although there were differences in regional localization and extent of expression. Thus, the initial response of the embryo is rapid with changes in expression of multiple genes observed within 1 h after ethanol exposure. Further, these differentially expressed mRNAs are candidates for modulating the type and extent of ethanol-induced damage in the developing CNS.