REGULATORY ELEMENTS OF NEUROTRANSMITTER-SPECIFIC GENES

神经递质特异性基因的调控元件

基本信息

批准号：
6024460
负责人：
CURTIS M LOER
金额：
$ 10.05万
依托单位：
UNIVERSITY OF SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-03-01 至 2004-02-28
项目状态：
已结题

项目摘要

DESCRIPTION (Adapted from applicant's abstract): To function correctly in the nervous system, a neuron must produce an appropriate neurotransmitter. Little is known about the mechanisms that govern this choice within developing neurons. Since the same neurotransmitters are used by organisms throughout the animal kingdom, genes regulating neurotransmitter choice are likely to be conserved among simple and complex organisms. Therefore, it is proposed to study this problem in a simple organism which is readily amenable to genetic and molecular analysis, the nematode worm Caenorhabditis elegans. This study will examine the regulation of neurotransmitter-specific genes expressed in serotonergic neurons ('serotonergic marker genes') of C. elegans. C. elegans genes necessary for serotonin synthesis and packaging: tryptophan hydroxylase, dopa decarboxylase, and vesicular monoamine transporter have been identified. It is proposed to 1) identify regulatory elements by comparing promoters of the homologous marker genes from a closely-related species and performing promoter deletion analyses, 2) identify regulatory genes by screening for mutants that do not express or mis-express the serotonergic marker genes. The long term goal of these studies is to understand how genes control the expression of specific neuronal identities, in particular, the neurotransmitter type of a neuron. Such studies may allow us to understand better why neurological disorders target specific subsets of neurons and ultimately to develop therapies to control the expression of neurotransmitters in specific cells of the human nervous system.

描述（改编自申请人的摘要）：在神经系统，神经元必须产生适当的神经递质。小的知道在发展中控制这种选择的机制神经元。由于生物在整个过程中使用相同的神经递质动物界，调节神经递质选择的基因可能是在简单和复杂的生物中保守。因此，提议在一个简单的生物体中研究这个问题，很容易被遗传和分子分析，线虫蠕虫秀丽隐杆线虫。这项研究将检查在中表达的神经递质特异性基因的调节秀丽隐杆线虫的血清素能神经元（“血清素能标记基因”）。秀丽隐杆线 5-羟色胺合成和包装所需的基因：色氨酸羟化酶，已鉴定出dopa脱羧酶和囊泡单胺转运蛋白。提议1）通过比较启动子来确定调节元素来自密切相关的物种和表演启动子的同源标记基因删除分析，2）通过筛选突变体来确定调节基因不要表达或误用血清素能标记基因。长期目标这些研究的是了解基因如何控制特定的表达神经元身份，特别是神经元的神经递质类型。这样的研究可能使我们可以更好地理解为什么神经系统疾病靶向神经元的特定子集，并最终开发用于控制的疗法神经递质在人类神经系统的特定细胞中的表达。