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

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初始效应不敏感或对乙醇急性耐受性的形成有关。该项目利用对乙醇初始效应不敏感或敏感的大鼠作为人类这种现象的模型。该项目旨在确定大鼠中负责这种反应的基因，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对人类的遗传风险因素负责。该研究利用数量性状基因座（QTL）确定的方法来定位这些基因在大鼠的基因组中。然后使用其他育种（同源菌株的开发）和分子生物学方法来关注这些基因所在的基因组的较窄区域。这将允许识别基因，并表明它们负责整个动物对乙醇的部分反应。然后将这些信息应用于人类研究，以预测影响人类酗酒风险的基因。然后才有可能制定预防或治疗战略。

项目成果

Differences in norepinephrine clearance in cerebellar slices from low-alcohol-sensitive and high-alcohol-sensitive rats.

低度酒精敏感和高度酒精敏感大鼠小脑切片去甲肾上腺素清除率的差异。

• DOI: 10.1016/s0741-8329(03)00098-3
• 发表时间: 2003
• 期刊: Alcohol (Fayetteville, N.Y.)
• 作者: Freund,RonaldK;Gerhardt,GregA;Marshall,KristeE;Palmer,MichaelR
• 通讯作者: Palmer,MichaelR

Short-term selection for acute ethanol tolerance and sensitization from an F2 population derived from the high and low alcohol-sensitive selectively bred rat lines.

对来自高和低酒精敏感选择性繁殖的大鼠品系的 F2 群体进行急性乙醇耐受和过敏的短期选择。

• DOI: 10.1016/j.alcohol.2007.10.001
• 发表时间: 2007
• 期刊: Alcohol (Fayetteville, N.Y.)
• 作者: Radcliffe,RichardA;Bludeau,Pequita;Deng,Xin-Sheng;Erwin,VGene;Deitrich,RichardA
• 通讯作者: Deitrich,RichardA

Putative role of brain acetaldehyde in ethanol addiction.

• DOI: 10.2174/1874473710801010003
• 发表时间: 2008
• 期刊: Current drug abuse reviews
• 作者: Xin-sheng Deng;R. Deitrich