CELL AND MOLECULAR EFFECTS OF ETHANOL IN LS AND SS MICE

描述：(改编自《调查者摘要》)胎儿酒精 在西方，综合征是导致智力低下的主要原因之一。 世界。酒精暴露对发育有广泛的影响。 神经系统影响的严重程度由任一数字介导 一个重要的因素是生物体的遗传组成。 为了评估遗传学在酒精S效应严重程度中的作用， 对重组自交系进行了以下两个实验 长睡眠和短睡眠的小鼠品系。这两个实验都将 检查暴露在单剂乙醇中的胚胎 胚胎第9天。第一个实验将检查来自 重组近交系长睡眠小鼠表现出不同程度的细胞死亡 与子宫内注射乙醇后短睡眠小鼠的胚胎进行比较 暴露在相同剂量的乙醇中。此外，这些实验将 检查胚胎的基因型别是否影响区域变异性 在细胞死亡的水平以及细胞死亡的手段是否通过 细胞凋亡。细胞死亡的水平将在以下部分进行量化 尼氏染色和一种新开发的缺口末端方法 标记濒临死亡的细胞，称为TUNEL。第二个实验将检验 信使核糖核酸(MRNA)表达的变化 差异显示。将在1、4、 酒精暴露后12小时。预计这项工作将 提供可能具有神经致畸作用或 神经保护作用。来帮助定义潜在的基因 这些影响、这些mRNAs的序列和定位将被研究 以及它们在敏感品系小鼠中的存在或不存在 或者对宫内酒精暴露的影响不敏感。

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.