CLONING OF A POTENTIAL REGULATOR OF THE DHAND FACTOR

Dhand 因子的潜在调节剂的克隆

• 批准号: 6536236
• 负责人: Mark W Russell
• 金额: $ 7.35万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6536236
• 关键词: arrhythmia; congenital heart disorder; developmental genetics; electrophoresis; embryo /fetus; functional /structural genomics; gene expression; genetic regulation; heart ventricle; in situ hybridization; laboratory mouse; molecular cloning; phosphorylation; polymerase chain reaction; posttranslational modifications; protein kinase; protein localization; protein structure function; tissue /cell preparation; transcription factor

DESCRIPTION (Adapted from applicant's description): Characterizing the molecular signaling cascade that directs cardiac ventricular maturation is vital to our understanding of normal cardiac development and may enable identification of the causes of congenital cardiac defects that affect ventricular structure or function. Abnormalities of ventricular development are associated with very high morbidity and mortality throughout the pre- and postnatal period. The goal of this laboratory is to characterize elements of the signaling cascade that direct right and left ventricular development by examining the function and regulation of the dHAND and eHAND basic helix-loop- helix (bHLH) transcription factors. These two factors appear to be vital elements in distinct regulatory pathways that direct right (dHAND) and left (eHAND) ventricular development. During preliminary studies in our laboratory, a novel kinase was identified that interacted with dHAND in a yeast two hybrid model. This kinase was strongly expressed in the developing and mature heart with limited expression in skeletal muscle. It has been localized to a region that is linked to an inherited developmental abnormality of ventricular structure and electrophysiologic function, arrhythmogenic right ventricular dysplasia (ARVD). This study will be a pilot project to characterize this novel gene, determine if it has a potential regulatory role in dHAND and/or eHAND function, and define its genomic structure in preparation for its evaluation as the gene responsible for one form of ARVD.

描述（根据申请人的描述改编）：表征 指导心室成熟的分子信号传导级联 对我们对正常心脏发展的理解至关重要，并可能使 识别影响先天性心脏缺陷的原因 心室结构或功能。心室发育异常 在整个前和 产后期。该实验室的目的是表征 通过 检查DHAND和EHAND基本螺旋环的功能和调节 螺旋（BHLH）转录因子。这两个因素似乎至关重要 在右右（dhand）的不同监管途径中的元素 （EHAND）心室发育。在我们实验室的初步研究中， 鉴定出一种新型激酶，该激酶与酵母两杂种中与dhand相互作用 模型。这种激酶在发育和成熟的心脏中强烈表达 骨骼肌表达有限。它已定位到一个地区 这与心室的遗传发育异常有关 结构和电生理功能，心律失常右心室 发育不良（ARVD）。这项研究将是一个试点项目，以表征这一点 新型基因，确定它在DHAND和/或是否具有潜在的调节作用 EHAND功能，并定义其基因组结构以准备 评估是负责一种ARVD的基因。