Analysis of Alcohol-Related Ingestive Behaviors in Mice

小鼠酒精相关摄入行为分析

• 批准号: 7235528
• 负责人: ALEXANDER A BACHMANOV
• 金额: $ 3.25万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-20 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7235528
• 关键词: 129 Mouse; Academy; Affect; Alcohol abuse; Alcohol consumption; Alcohols; Animal Model; Appetitive Behavior; Attention; Backcrossings; Behavioral; Candidate Disease Gene; Cloning; Collaborations; Congenic Mice; Congenic Strain; Consomic Strain; Consumption; Data; Economics; Ethanol; Feeding behaviors; Future; Generations; Genes; Genetic; Genome; Genome Scan; Genotype; Goals; Grant; Health; Human; Hybrids; Institutes; Intake; Laboratories; Lead; Link; Location; Maps; Methods; Modality; Mouse Strains; Mus; Numbers; Orthologous Gene; Perception; Phenotype; Physiology; Positioning Attribute; Predisposition; Procedures; Protocols documentation; Public Health; Quantitative Trait Loci; Research; Rewards; Role; Russia; Science; Scientist; Sensory; Staging; Sweetening Agents; Taste Perception; Testing; Trigeminal System; United States National Institutes of Health; Work; alcohol response; base; congenic; consomic; gene cloning; gene discovery; genetic linkage analysis; genome sequencing; hedonic; parent grant; parent project; preference; research study; response; size; sweet taste perception; tool

DESCRIPTION (provided by applicant): Excess consumption of ethanol (alcohol) imposes serious problems for human health and has major negative economic impact worldwide, and in the US and Russia especially. A predisposition towards alcohol overconsumption has a genetic component, and the discovery of the genes involved may lead to better control of alcohol consumption. Animal models can provide an efficient tool for discovering such genes. The long-term goal of the parent project is to positionally clone genes affecting voluntary ethanol consumption in C57BL/6ByJ (B6) and 129P3/J (129) mice. This involves developing congenic mouse strains to isolate genetic loci affecting ethanol consumption, and characterizing their behavioral responses to ethanol. The goals of the FIRCA proposal are to optimize experimental procedures and to conduct a comprehensive analysis of chemosensory perception of ethanol in the two parental strains, B6 and 129. To achieve this, we will characterize several aspects of chemosensory responsiveness to ethanol: hedonics, sensitivity, and taste quality perception. We will also examine the contribution of the gustatory, olfactory and trigeminal sensory inputs to the chemosensory responses elicited by ethanol. The most informative tests will then be used to study congenic and consomic mice created in the parent project. These experiments will test the hypothesis that differences between B6 and 129 mice in voluntary ethanol consumption depend in part on differential chemosensory perception of ethanol. The proposed studies will also elucidate the chemosensory modalities responsible for this differential perception. This will help us to elucidate mechanisms underlying the effects of the genetic loci, which will be useful for identification of corresponding candidate genes. Gene identification in mice will be followed by examination of the role of their human orthologs in future studies. This project will set the stage for a long-term collaboration between scientists at the Monell Center and the Pavlov Institute, and will help to build research capabilities at the Pavlov Institute. This research will be done primarily in Russia at the Pavlov Institute of Physiology of the Russian Academy of Sciences in collaboration with Dr. Zolotarev as an extension of the NIH grant # R01 AA011028 of Dr. Bachmanov. Relevance to public health: The goal of this project is to discover genes affecting alcohol consumption, which will lead to better understanding and control of alcohol abuse.

描述(申请人提供)：乙醇(酒精)的过量消费对人类健康造成了严重的问题，并对世界各地，特别是美国和俄罗斯产生了重大的负面经济影响。过度饮酒的倾向有遗传成分，相关基因的发现可能会导致更好地控制饮酒。动物模型可以为发现这样的基因提供一个有效的工具。母项目的长期目标是在C57BL/6ByJ(B6)和129P3/J(129)小鼠中定位克隆影响自愿酒精消耗的基因。这包括开发同种小鼠品系来分离影响酒精消费的遗传基因，并表征它们对酒精的行为反应。FIRCA提案的目标是优化实验程序，并对两个亲本菌株B6和129对乙醇的化学感觉进行全面分析。为了实现这一点，我们将表征对乙醇的化学感觉反应的几个方面：快乐性、敏感性和味觉质量感知。我们还将研究味觉、嗅觉和三叉神经感觉输入对乙醇引起的化学感觉反应的贡献。然后，最具信息量的测试将用于研究母项目中创造的同源和共生小鼠。这些实验将检验这样一个假设，即B6和129小鼠在自愿饮酒方面的差异部分取决于对酒精的不同化学感觉。拟议的研究还将阐明导致这种差异知觉的化学感觉模式。这将有助于我们阐明遗传座位效应的潜在机制，这将有助于识别相应的候选基因。在小鼠的基因鉴定之后，将检查它们的人类同源基因在未来研究中的作用。该项目将为莫内尔中心和巴甫洛夫研究所的科学家之间的长期合作奠定基础，并将有助于建立巴甫洛夫研究所的研究能力。这项研究将主要在俄罗斯的俄罗斯科学院巴甫洛夫生理学研究所与佐洛塔雷夫博士合作进行，作为巴赫马诺夫博士的NIH#R01 AA011028号拨款的延伸。与公众健康相关：该项目的目标是发现影响酒精消费的基因，这将导致更好地理解和控制酒精滥用。