CELL AND MOLECULAR EFFECTS OF ETHANOL IN LS AND SS MICE

描述：（改编自研究者摘要）胎儿酒精 综合征是西方智力迟钝的主要原因之一 世界 乙醇暴露对发育中的 神经系统的严重性与任何介导的影响的数量 一个重要的因素是生物体的遗传组成。 为了评估遗传学在乙醇影响严重性中的作用， 将对重组近交系进行以下2个实验 睡眠时间长和睡眠时间短的老鼠。 这两个实验都将 检查胚胎已经暴露在一个单一的乙醇团上， 胚胎第9天。 第一个实验将检查来自 重组近交长睡眠小鼠表现出不同程度的细胞死亡 与子宫内乙醇后短睡眠小鼠的胚胎相比， 暴露在相同剂量的乙醇中。 此外，这些实验将 检查胚胎的基因型是否影响区域变异性 以及细胞死亡的方式是否是通过 凋亡 将在具有以下特征的切片中定量细胞死亡水平： 用尼氏染色和最近开发的用于切口末端的方法染色 标记死亡细胞，称为TUNEL。 第二个实验将检查 信使RNA（mRNA）表达的变化， 差异显示 mRNA表达的变化将在1，4， 和乙醇暴露后12小时。 预计这项工作将 提供可能具有神经致畸性的候选mRNA或 神经保护作用。 以帮助确定潜在的基因， 这些影响，这些mRNA的序列和定位将被检查 以及它们在敏感的小鼠品系中的存在与否 或对子宫内乙醇暴露的影响不敏感。

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.