GENES FOR ETOH SENSITIVITY IN THE RAT--QTL ANALYSIS

Schuckit最近的发现指出了初始敏感性/急性耐受性 作为酒精中毒后续发展的重要预测因素， 年轻的男性。生物化学和生理学的显著相似性 乙醇的反应以及基因组之间的相似性 老鼠，老鼠和人，提供了罗塞塔石碑， 基因是导致人类酗酒风险增加的原因。 这项提议旨在发现哪些基因负责 大鼠对乙醇的初始敏感性（高和低酒精敏感性 线），并将研究结果与其他酒精大鼠模型进行比较 偏好（偏好和非偏好大鼠和高度酒精依赖大鼠） 低酒精依赖大鼠，由T-K博士开发。Li）以及与 初始敏感性的小鼠模型（来自美国的短睡眠和长睡眠小鼠） 行为遗传学研究所）和小鼠急性耐受模型 欧文博士正在开发（高酒精功能耐受性和 低酒精功能耐受小鼠）。 如果一个基因与人类的酒精反应有关， 在小鼠和大鼠体内都发现了显著增加。另一方面，在一项研究中， 大鼠和小鼠在乙醇中存在实质性差异， 相关的反应，但在这一点上，我们不知道哪个更密切 类似于人类的状况。 这一直是乙醇作用遗传学研究的目标， 在过去的25年里，啮齿动物和这样做的工具现在就在手边。

Recent findings by Schuckit point to initial sensitivity/acute tolerance as an important predictor of the subsequent development of alcoholism in young males. The marked similarity of biochemical and physiological reactions to ethanol as well as the similarity of the genome between mouse, rat and man, provides the Rosetta stone for discovering which genes are responsible for increased risk for alcoholism in man. This proposal is designed to discover which genes are responsible for initial sensitivity to ethanol in the rat (High and Low alcohol Sensitive lines) and compare the findings with other rat models of alcohol preference (Preference and NonPreference rats and High Alcohol Dependent and Low Alcohol Dependent rats, developed by Dr. T-K. Li) as well as with a mouse model of initial sensitivity (Short and Long Sleep mice from the Institute for Behavioral Genetics) and the acute tolerance model in mice under development by Dr. Erwin (the High Alcohol Function Tolerance and Low Alcohol Functional Tolerance mice). The likelihood that a gene is involved in alcohol reactions in man if it is found in both mice and rats is greatly increased. On the other hand, there are substantial differences between rats and mice in ethanol related reactions but at this point we do not know which more closely resembles the human condition. This has been the goal of studies of genetics of ethanol actions in rodents for the last 25 years and the tools for doing so are now at hand.