PROMOTER CHARACTERIZATION OF THE CART GENE

Cart 基因的启动子特征

基本信息

批准号：
8172327
负责人：
MICHAEL J KUHAR
金额：
$ 4.39万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2011-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8172327
关键词：
Behavioral Binding Biological Assay Brain region CREB1 gene Cocaine Computer Retrieval of Information on Scientific Projects Database Funding Gene Expression Genes Grant Injection of therapeutic agent Institution Laboratories Nucleus Accumbens Regulation Research Research Personnel Research Project Grants Resources Site Source United States National Institutes of Health Work cocaine- and amphetamine-regulated transcript protein in vivo promoter research study

Behavioral Binding Biological Assay Brain region CREB1 gene Cocaine Computer Retrieval of Information on Scientific Projects Database Funding Gene Expression Genes Grant Injection of therapeutic agent Institution Laboratories Nucleus Accumbens Regulation Research Research Personnel Research Project Grants Resources Site Source United States National Institutes of Health Work cocaine- and amphetamine-regulated transcript protein in vivo promoter research study

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项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is the main research project in our laboratory where regulation of CART gene expression has been a focus. We previously showed that over expression of CREB in the N Acc increased expression of CART peptide and we found that CREB is an in vivo regulator of CART expression which appears to be a mechanism of the action of cocaine. CART peptide acts as a homeostatic regulator and tends to oppose the action of cocaine in the nucleus accumbens. In the past period, we have shown using ChIP assays that CREB and P-CREB bind to the region of the CART promoter that contains the CRE site, suggesting a direct effect of CREB on the CART gene. Additional work supported has been the identification of siRNAs that reduce CART peptide levels after in vivo injection. Several siRNAs have been found that, in preliminary experiments, reduce CART peptide levels. This is important because until now there has been no way to acutely and abruptly reduce CART peptide levels in brain regions. Useful behavioral studies can be carried out if CART peptide levels can be acutely reduced.

该副本是利用众多研究子项目之一由NIH/NCRR资助的中心赠款提供的资源。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构是对于中心，这不一定是调查员的机构。这是我们实验室中的主要研究项目，该项目对CART基因表达的调节一直是重点。我们先前表明，在N ACC中过度表达CREB的表达增加了CART肽的表达，我们发现CREB是CART表达的体内调节剂，似乎是可卡因作用的一种机制。 CART肽充当稳态调节剂，并且倾向于反对可卡因在伏伏核中的作用。在过去的时期，我们使用芯片测定法表明，Creb和P-Creb与包含CRE位点的CART启动子的区域结合，这表明CREB对CART基因产生了直接影响。支持的其他工作是鉴定体内注射后降低CART肽水平的siRNA。已经发现，在初步实验中，已经发现了一些siRNA降低卡特肽水平。这很重要，因为到目前为止，还没有办法急剧和突然降低大脑区域的CART肽水平。如果可以急性降低CART肽水平，则可以进行有用的行为研究。