Genetic Study of a Novel Gene Involved in Neurotransmitter Transport

描述(申请人提供)：这项工作的目标是了解神经递质运输的调节以及运输与突触传递和神经疾病(如帕金森氏病和神经退行性变)的关系。以前的工作在果蝇中发现了一个参与神经递质运输的新基因。该基因已在小鼠体内克隆，命名为Lrrc50。这项研究的目的是了解这种新发现的基因Lrrc50在小鼠身上的功能。为了进行这些研究，正在使用现代遗传学方法在小鼠的大脑和眼睛中设计Lrrc50基因的区域特定突变。将使用电生理学、解剖学和行为学方法研究Lrrc50基因在携带Lrrc50基因大脑和眼睛特异突变的小鼠中的功能。在之前的工作中，一只小鼠被基因工程改造成了一种有花蕾的Lrrc50基因。通过将这种Lrrc50小鼠与由大脑或眼睛特异性启动子驱动的表达Cre重组酶的小鼠交配，已经获得了Lrrc50基因的区域敲除。递质的循环和运输对于正常的突触传递是至关重要的，但对调节突触功能的分子却知之甚少。精神疾病、阿尔茨海默病、学习障碍和智力低下等疾病被认为是突触的疾病。这一建议的创新是基于我们发现了一种参与递质运输的新基因，并利用现代遗传学在小鼠和果蝇身上进行了研究。 与公共健康相关：递质回收和运输对于神经细胞之间的正常通讯至关重要，但人们对调节递质回收和运输的分子知之甚少。精神疾病、阿尔茨海默病、学习障碍和智力低下等疾病被认为是神经细胞或突触之间通信系统的疾病。这一提议的创新是基于我们发现了一种参与递质运输的新基因，并使用了现代基因工程。

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.