Genetic Study of a Novel Gene Involved in Neurotransmitter Transport

参与神经递质运输的新基因的遗传学研究

• 批准号: 8041090
• 负责人: STEPHEN FOX HEINEMANN
• 金额: $ 23.57万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-10 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8041090
• 关键词: Alzheimer' s Disease; Behavioral; Brain; Communication; Disease; Drosophila genus; Engineering; Eye; Genes; Genetic; Genetic Engineering; Goals; Health; Learning; Learning Disabilities; Memory; Mental Retardation; Mental disorders; Methods; Mus; Mutation; Names; Nerve Degeneration; Neurons; Neurotransmitters; Parkinson Disease; Partner in relationship; Proteins; Recycling; Regulation; Research; Synapses; Synaptic Transmission; System; Testing; Work; analog; base; gene discovery; innovation; nervous system disorder; neurotransmitter transport; novel; promoter; recombinase; synaptic function

DESCRIPTION (provided by applicant): The goal of this work is to understand the regulation of neurotransmitter transport and the relationship of transport to synaptic transmission and neurological diseases such as Parkinson's Disease and neurodegeneration. Previous work identified a novel gene in Drosophila (dtr) that is involved in neurotransmitter transport. This gene has been cloned in mouse and named Lrrc50. The goal of this research is to understand the function of this newly discovered gene called Lrrc50 in the mouse. To undertake these studies modern genetic methods are being used to engineer mice with regional specific mutations of the Lrrc50 gene in the brain and in the eye. Electrophysiological, anatomical and behavioral methods will be used to study the function of the Lrrc50 gene in the mouse carrying brain and eye specific mutations of the Lrrc50 gene. In previous work a mouse has been genetically engineered with a floxed Lrrc50 gene. By mating this floxed Lrrc50 mouse to mice expressing the Cre recombinase driven by a brain or eye specific promoter regional knock-outs of the Lrrc50 gene have been obtained. Transmitter recycling and transport is critical for normal synaptic transmission yet little is known about the molecules that regulate synaptic function. Diseases such as mental illness, Alzheimer's disease, learning disabilities and mental retardation are thought to be diseases of the synapse. The innovation of this proposal is based upon our discovery of a novel gene involved in transmitter transport and the use of modern genetics in mouse and Drosophila. PUBLIC HEALTH RELEVANCE: Transmitter recycling and transport is critical for normal communication between nerve cells yet little is known about the molecules that regulate transmitter recycling and transport. Diseases such as mental illness, Alzheimer's disease, learning disabilities and mental retardation are thought to be diseases of the communication system between nerve cells or the synapse. The innovation of this proposal is based upon our discovery of a novel gene involved in transmitter transport and the use of modern genetic engineering.

描述（由申请人提供）：这项工作的目标是了解神经递质转运的调节以及转运与突触传递和神经系统疾病（如帕金森病和神经变性）的关系。先前的工作在果蝇中发现了一个新的基因（dtr），它参与神经递质的运输。该基因已在小鼠中克隆，并命名为Lrrc50。这项研究的目的是了解这个新发现的基因Lrrc50在小鼠中的功能。 为了进行这些研究，现代遗传学方法正在被用来改造小鼠的大脑和眼睛中Lrrc50基因的区域特异性突变。将使用电生理学、解剖学和行为学方法来研究Lrrc50基因在携带Lrrc50基因的脑和眼特异性突变的小鼠中的功能。在先前的工作中，小鼠已经被基因工程改造成具有floxed Lrrc50基因。通过将该floxed Lrrc50小鼠与表达由脑或眼特异性启动子驱动的Cre重组酶的小鼠交配，获得了Lrrc50基因的区域敲除。 递质的回收和转运对于正常的突触传递至关重要，但人们对调节突触功能的分子知之甚少。诸如精神疾病、阿尔茨海默病、学习障碍和智力迟钝等疾病被认为是突触疾病。这一提议的创新是基于我们发现了一种参与递质转运的新基因，以及现代遗传学在小鼠和果蝇中的应用。 公共卫生关系：递质的回收和运输对于神经细胞之间的正常通信至关重要，但人们对调节递质回收和运输的分子知之甚少。诸如精神疾病、阿尔茨海默病、学习障碍和智力迟钝等疾病被认为是神经细胞或突触之间的通信系统的疾病。这一建议的创新是基于我们发现了一个新的基因参与传递和现代基因工程的使用。