CELL AND MOLECULAR EFFECTS OF ETHANOL IN LS AND SS MICE

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DESCRIPTION: (Adapted from the Investigator's Abstract) Fetal alcohol syndrome is one of the leading causes of mental retardation in the western world. Ethanol exposure has a wide range of effects on the developing nervous system with the severity of the effects mediated by any of a number of factors; one important factor is the genetic composition of the organism. To asses the role of genetics in the severity of ethanol s effects, the following 2 experiments will be conducted on the recombinant inbred long-sleep and short-sleep strains of mice. Both of these experiments will examine embryos that have been exposed to a single bolus of ethanol on embryonic day 9. The first experiment will examine whether embryos from recombinant inbred long-sleep mice exhibit different levels of cell death compared to embryos from short-sleep mice following in utero ethanol exposure to the same dose of ethanol. Further, these experiments will examine whether the genotype of the embryo affects the regional variability in the levels of cell death and whether the means of cell death is through apoptosis. The level of cell death will be quantified in sections that have been stained with a Nissl stain and a recently developed method for nick-end labeling dying cells, termed TUNEL. The second experiment will examine the changes in messenger RNA (mRNA) expression using the technique of differential display. Changes in mRNA expression will be examined at 1, 4, and 12 hours after ethanol exposure. It is anticipated that this work will provide candidate mRNAs that have possible neuroteratogenic or neuroprotective effects. To assist in defining potential genes that have these effects, the sequence and localization of these mRNAs will be examined as well as their presence or absence in strains of mice that are sensitive or insensitive to the effects of in utero ethanol exposure.