SELECTION OF LINES FOR ETHANOL THERMAL SENSITIVITY

拟议的选择性育种研究的主要长期目标是 揭示了一个普遍存在的，容易评估的对乙醇的反应 （体温过低），这是有用的敏感性，耐受性和 摆脱对乙醇的身体依赖。 我们一直在开发一种 对EtOH诱导的HT的遗传易感性的动物模型。 使用 家系内选择育种，选择了品系和重复 3 g/kg给药后对急性HT的敏感性（冷）和抵抗性（热） 乙醇 继续成功地选择拟议的路线， 提供了一个急需的遗传标记，用于预测对 形成乙醇身体依赖。 拟议实验的第一个目标是继续开发 热和冷选择线，直到对选择的反应明显 达到了最大值。 在这一点上，酒精易感基因 敏感性大概已经固定在纯合状态。 的 第二个目标是确定HT反应的遗传相关性。 一 除EtOH诱导的HT外，对EtOH的行为反应数量，以及 对其他假定共享，或不共享， 乙醇的作用机制将在热和冷线进行比较 在整个选择过程中每4代。 作为验证的第二种方法， 相关的选择反应，胚胎从线将被冷冻， 在整个过程中定期保存遗传资源， 选择. 每4代冻存胚胎的存在 将允许随后测试相关响应， 选择. 实际上，可以做一个横截面实验， 概括了选择程序的发展过程。 冷冻保存也将提供一个必要的保险政策， 由于火灾、传染性、 疾病，“动物权利”活动或其他灾难性损失。 额外 这些品系的原种将被繁殖，并提供给研究人员， 希望进行机制导向的实验，以阐明 酒精中毒的生理和/或生化基础。

The major long-term goal of the proposed selective breeding study is to shed light on an ubiquitous, easily assessed response to ethanol (hypothermia) that is useful as an index of sensitivity, tolerance and withdrawal from physical dependence on EtOH. We have been developing an animal model of genetic susceptibility to EtOH-induced HT. Using within-family selective breeding, lines and replicates have been selected for susceptibility (COLD) and resistance (HOT) to acute HT after 3 g/kg EtOH. The continued successful selection of the proposed lines could provide a much-needed genetic marker for predicting the susceptibility to develop ethanol physical dependence. The first goal of the proposed experiments is to continue to develop the HOT and COLD selected lines until response to selection has apparently reached its maximum. At this point, genes predisposing for alcohol sensitivity will presumably have been fixed in the homozygous state. The second goal is to determine genetic correlates of the HT response. A number of behavioral response to EtOH other than EtOH-induced HT, and hypothermic response to other agents postulated to share, or not to share, ethanol's mechanism of action will be compared in the HOT and COLD lines each 4 generations throughout selection. As a second method for verifying correlated response to selection, embryos from the lines will be frozen to preserve the genetic stock at regular intervals during the course of selection. The existence of cryopreserved embryos from each 4 generations of selection will allow subsequent testing for correlated responses to selection. In effect, a cross-sectional experiment can be done which recapitulates the developmental progress of the selection program. Cryopreservation will also provide an essential insurance policy against the possibility of loss of the COLD and HOT lines due to fire, infectious disease, "animal rights" activism, or other catastrophic loss. Additional stock of the lines will be bred and be made available for researchers who wish to perform mechanism-oriented experiments to elucidate the physiological and/or biochemical basis for alcoholism.