Epistatic Modifiers and Novel Genetic Contributions to Binge-like Drinking and Motivational Effects of Alcohol
上位调节剂和新的遗传因素对酗酒和酒精的激励作用
基本信息
- 批准号:9258212
- 负责人:
- 金额:$ 5.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-09-23 至 2019-09-22
- 项目状态:已结题
- 来源:
- 关键词:AccountingAffectAgonistAlcohol PhenotypeAlcohol consumptionAlcoholismAlcoholsAnimal GeneticsAnimal ModelAnimalsAttenuatedBehavioralBehavioral GeneticsBiologicalBloodBreedingCandidate Disease GeneComplexDataDevelopmentDiseaseEnvironmental Risk FactorEnzymesEthanolEtiologyFellowshipGene-ModifiedGenesGeneticGenetic RiskGenetic TechniquesGenotypeGlycolysisGoalsHeavy DrinkingInbred MouseInbred StrainInbred Strains MiceIndividualInjection of therapeutic agentIntakeIntoxicationLactoylglutathione LyaseMapsMeasuresMusMutant Strains MiceNational Institute on Alcohol Abuse and AlcoholismPatternPhenotypePredispositionPreventionProceduresPropertyPyruvaldehydeQuantitative GeneticsQuantitative Trait LociResearch DesignResistanceRewardsRiskRodentRoleSelf StimulationSocietiesStructureTaste aversionTechniquesTestingTrainingTransgenesalcohol effectalcohol misusealcohol researchalcohol rewardalcohol sensitivityalcohol use disorderalcoholism therapybasebinge drinkingcostdensitydesigndrinkingdrinking behaviorfollow-upgene interactiongenetic manipulationgenetic risk factorgenome wide association studyhedonicinhibitor/antagonistinnovationknock-downmouse modelnovelnovel strategiesoffspringoverexpressionphenotypic datapreventreceptorresearch studyrisk variant
项目摘要
Project Summary
Alcohol use disorders (AUDs) are associated with significant costs to both the individual and society. Genetic
and environmental factors contribute to the risk of AUDs and excessive drinking, and a better understanding of
the specific risk genes will allow for novel strategies for prevention and treatment. Glyoxalase 1 (GLO1) is a
new target in alcohol research identified previously by rodent studies in our lab. Overexpression of Glo1
increases binge-like drinking in mice, suggesting involvement in excessive alcohol intake. The endogenous
substrate of GLO1, methylglyoxal (MG), acts as a partial agonist at GABAA receptors. Pharmacological and
genetic manipulations that increase MG levels (i.e. GLO1 inhibition, Glo1 gene knockdown) have been shown
to reduce binge-like drinking in mice, providing a possible mechanism through which GLO1 modifies alcohol
consumption. The goal of this fellowship project is to determine the role of Glo1 and other potential related
genetic risk factors for excessive drinking in a mouse model of binge-like intake. Aim 1 will use a novel
breeding strategy to generate an F1 panel of inbred mice overexpressing Glo1 on different genetic
backgrounds. These mice will be phenotyped for alcohol binge-like drinking. A two-part genome wide
association study will be used to 1) map epistatic modifiers of Glo1 that enhance or suppress its effects on
alcohol drinking, and 2) identify potential quantitative trait loci associated with binge-like drinking. Aim 2 will
investigate why Glo1 modifies alcohol intake, by testing the hypothesis that changes in Glo1 expression alter
sensitivity to the reward-enhancing effects of alcohol or alcohol aversion. Together, these experiments will give
us a better understanding of how Glo1 overexpression contributes to risk of excessive drinking, and will
highlight other genes that modify this risk. This dual approach may identify novel targets and strategies for
preventing or treating drinking to intoxication
项目摘要
酒精使用障碍(AUD)与个人和社会的重大成本有关。遗传
和环境因素有助于AUDs和过量饮酒的风险,
特定的风险基因将允许新的预防和治疗策略。Glycoprotein 1(GLO1)是一种
酒精研究中的新目标,以前在我们实验室的啮齿动物研究中确定。Glo1过表达
增加了小鼠的狂饮,表明与过量酒精摄入有关。内生
GLO1的底物甲基乙二醛(MG)作为GABAA受体的部分激动剂。药理学和
已经显示了增加MG水平的遗传操作(即GLO 1抑制、GLO 1基因敲低
减少小鼠的狂饮,提供了GLO1调节酒精的可能机制。
消费这个研究项目的目标是确定Glo1和其他潜在的相关基因的作用。
遗传风险因素过量饮酒的小鼠模型的暴饮暴食。目标1将使用一本小说
产生在不同遗传学上过表达Glo1的近交系小鼠的F1组的育种策略
背景将对这些小鼠进行酗酒样饮酒的表型分析。两部分基因组
关联研究将用于:1)映射Glo1的上位性修饰物,其增强或抑制Glo1的作用,
饮酒,和2)确定潜在的数量性状基因座与狂饮。目标2将
研究为什么Glo1改变酒精摄入量,通过测试Glo1表达的变化改变酒精摄入量的假设,
对酒精或酒精厌恶的奖励增强效应的敏感性。总之,这些实验将给
我们更好地了解Glo1过度表达如何导致过度饮酒的风险,
突出显示了改变这种风险的其他基因。这种双重方法可以确定新的目标和战略,
预防或治疗饮酒中毒
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Amanda Malina Barkley-Levenson其他文献
Amanda Malina Barkley-Levenson的其他文献
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{{ truncateString('Amanda Malina Barkley-Levenson', 18)}}的其他基金
Identification and Characterization of Novel Genetic Mechanisms in Alcohol Use Disorder and Excessive Drinking
酒精使用障碍和过量饮酒的新遗传机制的鉴定和表征
- 批准号:
10701871 - 财政年份:2022
- 资助金额:
$ 5.25万 - 项目类别:
Identification and Characterization of Novel Genetic Mechanisms in Alcohol Use Disorder and Excessive Drinking
酒精使用障碍和过量饮酒的新遗传机制的鉴定和表征
- 批准号:
10614148 - 财政年份:2022
- 资助金额:
$ 5.25万 - 项目类别:
Identification and Characterization of Nobel Genetic Mechanisms in Alcohol Use Disorder and Excessive Drinking
酒精使用障碍和过度饮酒的诺贝尔遗传机制的鉴定和表征
- 批准号:
10399924 - 财政年份:2021
- 资助金额:
$ 5.25万 - 项目类别:
Identification and Characterization of Novel Genetic Mechanisms in Alcohol Use Disorder and Excessive Drinking
酒精使用障碍和过量饮酒的新遗传机制的鉴定和表征
- 批准号:
10018802 - 财政年份:2019
- 资助金额:
$ 5.25万 - 项目类别:
Identification and Characterization of Novel Genetic Mechanisms in Alcohol Use Disorder and Excessive Drinking
酒精使用障碍和过量饮酒的新遗传机制的鉴定和表征
- 批准号:
9806313 - 财政年份:2019
- 资助金额:
$ 5.25万 - 项目类别:
The role of neuropeptide Y in binge-like drinking in mice
神经肽 Y 在小鼠暴饮暴食中的作用
- 批准号:
8856438 - 财政年份:2013
- 资助金额:
$ 5.25万 - 项目类别:
The role of neuropeptide Y in binge-like drinking in mice
神经肽 Y 在小鼠暴饮暴食中的作用
- 批准号:
8583261 - 财政年份:2013
- 资助金额:
$ 5.25万 - 项目类别:
The role of neuropeptide Y in binge-like drinking in mice
神经肽 Y 在小鼠暴饮暴食中的作用
- 批准号:
8453775 - 财政年份:2013
- 资助金额:
$ 5.25万 - 项目类别:
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