Selective Breeding for Ethanol Sensitivity

乙醇敏感性的选择性育种

• 批准号: 7660743
• 负责人: RICHARD A DEITRICH
• 金额: $ 3.03万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-18 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7660743
• 关键词: Acute; Affinity; Alcoholism; Animals; Backcrossings; Biological; Blood; Brain; Breeding; Congenic Strain; Development; Dose; Ethanol; Generations; Genes; Genetic; Genetic Risk; Genome; Genotype; Human; Human Genome; Inbred Strain; Individual Differences; Lod Score; Maps; Measures; Mediating; Methods; Midbrain structure; Modeling; Molecular; Mus; Neurotensin; Nucleus Accumbens; Performance; Phenotype; Prevention; Progress Reports; Quantitative Trait Loci; Rattus; Recombinant Inbred Strain; Recombinants; Research; Resources; Risk; Sleep; Synteny; Testing; Time; alcohol effect; alcohol response; alcohol sensitivity; congenic; design; fighting; genetic risk factor; hypnotic; pleiotropism; putamen; rat genome; receptor density; response; retinal rods; size; Acute; Affinity; Alcoholism; Animals; Backcrossings; Biological; Blood; Brain; Breeding; Congenic Strain; Development; Dose; Ethanol; Generations; Genes; Genetic; Genetic Risk; Genome; Genotype; Human; Human Genome; Inbred Strain; Individual Differences; Lod Score; Maps; Measures; Mediating; Methods; Midbrain structure; Modeling; Molecular; Mus; Neurotensin; Nucleus Accumbens; Performance; Phenotype; Prevention; Progress Reports; Quantitative Trait Loci; Rattus; Recombinant Inbred Strain; Recombinants; Research; Resources; Risk; Sleep; Synteny; Testing; Time; alcohol effect; alcohol response; alcohol sensitivity; congenic; design; fighting; genetic risk factor; hypnotic; pleiotropism; putamen; rat genome; receptor density; response; retinal rods; size

DESCRIPTION (provided by applicant): Genetic risk for development of alcoholism in humans has been shown to be related to insensitivity to the initial effects of ethanol or to the development of acute tolerance to ethanol. This project utilizes rats that have been selectively bred for insensitivity or sensitivity to the initial effects of ethanol as a model of this phenomenon in humans. The project seeks to identify the genes responsible for this response in rats, to compare these results with similar studies in other rat selection studies and in mice to predict which genes may be responsible for the genetic risk factors in humans. The research utilizes methods of Quantitative Trait Loci (QTL) determination to locate these genes within the genome of the rat. Other breeding (development of congenic strains) and molecular biological methods are then used to focus on a narrower region of the genome in which these genes reside. This will allow the identification of the genes and show that they are responsible for a portion of the response to ethanol in the whole animal. This information is then applied to studies in humans to predict where genes will be found that influence the risk of development of alcoholism in humans. Development of prevention or treatment strategies will then be possible.

描述（由申请人提供）：已证明人类酒精中毒的遗传风险与对乙醇的初始影响或对乙醇的急性耐受性的发育无敏。该项目利用已选择性繁殖的大鼠对乙醇作为人类现象的模型的初始作用不敏感或敏感性。该项目旨在确定对大鼠中这种反应的基因，将这些结果与其他大鼠选择研究和小鼠中的类似研究进行比较，以预测哪些基因可能是人类遗传危险因素的原因。该研究利用定量性状基因座（QTL）测定方法将这些基因定位在大鼠的基因组中。然后使用其他育种（先天性菌株的发展）和分子生物学方法来专注于这些基因所在的基因组的狭窄区域。这将允许鉴定基因，并表明它们负责整个动物中对乙醇的一部分。然后将这些信息应用于人类的研究，以预测将发现在哪里影响人类酒精中毒风险的基因。这样就可以制定预防或治疗策略。