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Identification of modifiers of the dopamine transporter.

多巴胺转运蛋白修饰剂的鉴定。

基本信息

批准号：
9019136
负责人：
DAVID Joseph SPECA
金额：
$ 7.85万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
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：
2016-05-01 至 2018-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9019136
关键词：
Attention deficit hyperactivity disorder Biological Phenomena Biology Bipolar Depression Bipolar Disorder Brain Carrier Proteins Chromosomes, Human, Pair 18 Co-Immunoprecipitations Complementary DNA Complex Disease Dopamine Drug Addiction Enhancers Financial compensation Functional disorder Genes Genetic Genetic Screening Genomics Homeostasis In Vitro Induced Mutation Institutes Lead Maps Mass Spectrum Analysis Mental Depression Mental disorders Mind Molecular Mus Mutagenesis Mutant Strains Mice Mutate Mutation Parkinson Disease Point Mutation Quantitative Trait Loci Regulation Schizophrenia Susceptibility Gene System Testing Validation Yeasts dopamine transporter drug development exome sequencing forward genetics gene product mouse genome mutant mutation screening nervous system disorder neurotransmission next generation sequencing novel overexpression programs public health relevance screening trait yeast two hybrid system

项目摘要

DESCRIPTION (provided by applicant) Dysfunction of the dopaminergic system has been implicated in a variety of neurological disorders including schizophrenia, bipolar disorder and drug addiction. The dopamine transporter protein is a key regulator of dopaminergic homeostasis. Our long-term objective is to identify susceptibility genes involved in dopamine-regulated disorders. With this aim in mind, we performed a mouse forward mutagenesis screen to identify genetic interactions with the dopamine transporter. We have mapped a putative enhancer and suppressor of the dopamine transporter to chromosomes 18 and 16, respectively. In this proposal, we will employ whole exome sequencing to identify the causative mutations underlying these previously mapped loci. Identification of these modifiers will lead to a better understanding of dopamine regulation and may lead to novel treatments for a variety of neurological disorders.

描述（由申请人提供）多巴胺能系统的功能障碍与多种神经系统疾病有关，包括精神分裂症、双相情感障碍和药物成瘾。多巴胺转运蛋白是多巴胺能稳态的关键调节因子。我们的长期目标是确定与多巴胺调节的疾病有关的易感基因。考虑到这一目标，我们进行了小鼠正向诱变筛选，以确定与多巴胺转运蛋白的遗传相互作用。我们已经绘制了一个假定的多巴胺转运蛋白的增强子和抑制子，分别对染色体18和16。在这个建议中，我们将采用全外显子组测序来确定这些先前定位的基因座的致病突变。这些修饰剂的鉴定将导致更好地理解多巴胺调节，并可能导致各种神经系统疾病的新治疗方法。