Gene Targets of NKX 2.5 in the Conduction System

NKX 2.5在传导系统中的基因靶标

• 批准号: 6835441
• 负责人: MELVIN M SCHEINMAN
• 金额: $ 3.1万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6835441
• 关键词: arrhythmia; atrioventricular node; congenital heart disorder; developmental genetics; disease /disorder etiology; embryo /fetus; gene expression; genetic models; genetically modified animals; heart conduction system; heart electrical activity; heart ventricle; immunocytochemistry; in situ hybridization; laboratory mouse; mature animal; membrane channels; microarray technology; newborn animals; pathologic process; postdoctoral investigator; protein structure function; transcription factor

DESCRIPTION (provided by applicant): Mutations in gene encoding the homeobox transcription factor (NKX 2.5) have been found to cause human congenital cardiac disease manifested by structural cardiac changes (VSD, ASD) as well as AV block. Our hypothesis is that NKX 2.5 plays a critical role in regulation of gene expression for development of the cardiac conduction system. Using the Iox-P, Cre technology to develop and further characterize a mouse line with NKX 2.5 knockout, the proposed research plan is to identify the downstream targets of NKX 2.5 knockouts in the AV node and ventricular specialized conduction system utilizing gene expression microarray analyses. Finally, we plan to study the role of specific ion channels (i.e. MinK and HCN-1) in the pathogenesis of arrhythmias in the ventricular restricted knockout mouse model. This will be done by using in-situ hybridization and immunohistochemistry to follow the pattern of expression of these ion channels.

描述（由申请人提供）：已发现编码同源型转录因子的基因突变（NKX 2.5）引起人类先天性心脏病，其结构性心脏变化（VSD，ASD）以及AV阻滞。我们的假设是NKX 2.5在调节心脏传导系统发展基因表达中起着至关重要的作用。使用IOX-P技术，使用NKX 2.5敲除的小鼠线开发和进一步表征，拟议的研究计划是通过使用基因表达微阵列分析的AV节点和心室专业传导系统中NKX 2.5敲除的下游靶标。最后，我们计划研究特定离子通道（即Mink和HCN-1）在心室受限小鼠模型中心律不齐的发病机理中的作用。这将通过使用原位杂交和免疫组织化学来遵循这些离子通道的表达方式来完成。