An in vivo cellular model to study the biological effects of alcohol

研究酒精生物效应的体内细胞模型

• 批准号: 7289172
• 负责人: Su Guo
• 金额: $ 33.65万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7289172
• 关键词: Acute; Address; Adenylate Cyclase; Alcoholism; Alcohols; Animal Behavior; Appearance; Behavior; Behavioral; Behavioral Assay; Biological; Biological Assay; Brain; Calcium; Candidate Disease Gene; Catalytic Domain; Cell model; Cells; Chromosome Mapping; Chronic; Classification; Cloning; Complex; Condition; Cultured Cells; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Development; Disease; Ear; Environment; Ethanol; Fishes; Future; GTP-Binding Proteins; Genes; Genetic Screening; Goals; Heavy Drinking; Hormones; Human; Laboratories; Light; Measures; Mediating; Medical; Melanocyte stimulating hormone; Melanosomes; Molecular; Molecular Genetics; Mutagenesis; Mutation; Names; Neural Crest; Neuraxis; Neurotransmitters; Norepinephrine; Organelles; Pathway interactions; Pattern; Physiological; Physiological Processes; Process; Regulation; Research Personnel; Shapes; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Testing; Zebrafish; alcohol effect; alcohol exposure; alcohol response; alcoholism/alcohol abuse; base; gene function; genetic analysis; in vivo; insight; medical complication; melanin-concentrating hormone; melanocyte; mutant; novel; positional cloning; problem drinker; receptor; response

DESCRIPTION (provided by applicant): The goal of this project is to carry out a systematic genetic analysis in the zebrafish Danio rerio, to understand the biological effects of alcohol on cell signaling. Understanding the molecular mechanisms that mediate cellular responses to acute or chronic ethanol treatment is not only important for understanding the complex signal transduction pathways and their cross regulation inside cells, but is also critical for understanding alcoholism, alcohol abuse, and the medical complications of excessive drinking. Simple and robust assays have been developed in zebrafish to assess the effects of acute as well as chronic alcohol exposure on cell signaling. By using these simple and powerful assays, we have carried out a pilot mutagenesis screen and identified mutations that display abnormal responses to either acute or chronic treatment of ethanol. These molecular genetic analyses will provide fundamental insights into signal transduction mechanisms and its modulation by acute and chronic alcohol exposure. Future behavioral and pathophysiological analyses can be done using the isolated zebrafish mutants. Further, molecules identified in zebrafish will provide candidate genes for association study of human alcoholism and alcoholic medical disorders.

描述（由申请人提供）：该项目的目的是在斑马鱼Danio Rerio中进行系统的遗传分析，以了解酒精对细胞信号的生物学影响。了解介导细胞对急性或慢性乙醇治疗反应的分子机制不仅对于理解复杂的信号转导途径及其在细胞内部的交叉调节而言很重要，而且对于了解酒精中毒，酒精滥用和过量饮酒的医疗并发症也是至关重要的。斑马鱼已经开发了简单，健壮的测定，以评估急性和慢性酒精暴露对细胞信号的影响。通过使用这些简单而有力的测定，我们进行了一个试验诱变筛查，并确定了对乙醇急性或慢性治疗的异常反应的突变。这些分子遗传分析将提供对信号转导机制的基本见解及其通过急性和慢性酒精暴露的调节。可以使用孤立的斑马鱼突变体进行未来的行为和病理生理分析。此外，在斑马鱼中鉴定出的分子将为人类酒精中毒和酒精疾病的关联研究提供候选基因。