MAPPING OF ALCOHOL PREFERENCE GENES IN RQI STRAINS

RQI 菌株中酒精偏好基因的图谱

• 批准号: 2413270
• 负责人: Csaba Vadasz
• 金额: $ 14.65万
• 依托单位: NATHAN S. KLINE INSTITUTE FOR PSYCH RES
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2413270
• 关键词: alcoholic beverage consumption; animal genetic material tag; behavioral /social science research tag; behavioral genetics; dopamine; genetic markers; genetic polymorphism; genetic strain; genotype; high performance liquid chromatography; laboratory mouse; linkage mapping; microdialysis; molecular cloning; neuropharmacology; neurotransmitter transport; nucleus accumbens; phenotype; preference; quantitative trait loci

Unequivocal identification of Quantitative Trait Loci (QTLs) that affect behavioral traits has been difficult, with progress limited by the behavioral and genetic complexity of these phenotypes. To circumvent complicating factors such as the effects of more than one gene, genetic interaction, etc., our strategy is to take advantage of a new genetic analytical approach, the use of congenic Recombinant Quantitative-Trait- Loci Introgression (RQI) strains, developed in our laboratory by repeated backcross-intercross cycles with concomitant selection for mesencephalic tyrosine hydroxylase activity (TH/MES, an index of number of dopamine neurons) for the genetic dissection of the murine mesotelencephalic dopamine system. We will focus on alcohol preference and alcohol-induced dopamine release in the nucleus accumbens because dopamine has been implicated in the mechanisms of alcohol-related behaviors in rodents and our preliminary results indicated significant differences both in brain dopamine systems and in alcohol preference in the progenitor and RQI strains. The overall goal of the proposal is to map and clone genes that play a pivotal role in alcohol preference. Once the QTLs are mapped and the congenic RQI strains that carry alcohol preference-QTLs are identified, a further goal of the proposal is to study the mechanism of QTL-action on a homogeneous genetic background provided by the congenic RQI lines. Identification of human homolog genes offers the potential for prevention and treatment of alcohol abuse. Our specific aim is (a) to map alcohol preference QTLs in sets of congenic Recombinant Quantitative- Trait-Loci introgression strains by analyzing the distribution and polymorphic microsatellite markers in the strains and investigating correlations between the markers and alcohol preference measured in a limited access paradigm, and (b) to investigate the effect of alcohol on nucleus accumbens dopamine function by in vivo microdialysis in congenic RQI strains with genetically determined high, intermediate and low alcohol preference.

影响影响的定量性状基因座（QTL）的明确鉴定 行为特征很困难，进步受到 这些表型的行为和遗传复杂性。 绕开 复杂因素，例如多个基因的遗传的影响 互动等，我们的策略是利用一种新的遗传 分析方法，使用先天性重组定量特征 基因座渗入（RQI）菌株，通过重复在我们的实验室中开发 与中脑的伴随选择的反向交叉中间循环 酪氨酸羟化酶活性（TH/MES，多巴胺数量的指数 神经元）用于鼠介脑的遗传解剖 多巴胺系统。 我们将专注于酒精偏好和酒精引起的 多巴胺在伏隔核中释放，因为多巴胺一直是 与啮齿动物中酒精相关行为的机制有关 我们的初步结果表明大脑的显着差异 多巴胺系统以及祖细胞和RQI的酒精偏好 菌株。 该提案的总体目标是映射和克隆基因 在酒精偏爱中起关键作用。 QTL映射后， 鉴定出携带酒精偏好QTL的Encenic RQI菌株被鉴定出来， 该提案的另一个目标是研究QTL-action的机制 先天性RQI线提供的同质遗传背景。 人类同源基因的鉴定提供了预防的潜力 和滥用酒精的治疗。 我们的具体目的是（a）绘制酒精 优先QTL中的QTL集中的QTL集 通过分析分布和多态性来渗入菌株 菌株中的微卫星标记并研究相关性 在有限访问中测得的标记和酒精偏好之间 范式和（b）研究酒精对伏拟核的影响 同类RQI菌株中体内微透析的多巴胺功能 遗传确定的高，中间和低酒精偏好。