CLONING OF A POTENTIAL REGULATOR OF THE DHAND FACTOR

描述（改编自申请人的描述）： 指导心室成熟的分子信号级联反应， 对我们理解正常心脏发育至关重要， 先天性心脏病的病因， 心室结构或功能。心室发育中止 与整个产前和产后期间非常高的发病率和死亡率有关， 产后时期这个实验室的目标是描述 信号级联通过以下方式指导左右心室发育： 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 在不同的调控途径，直接右（dHAND）和左的元素 （eHAND）心室发育。在我们实验室的初步研究中， 在酵母双杂交系统中鉴定出一种与dHAND相互作用的新激酶 模型这种激酶在发育和成熟的心脏中强烈表达 在骨骼肌中表达有限。它已经被定位到一个区域 与先天性心室发育异常有关 致心律失常性右心室结构和电生理功能 发育不良（ARVD）。这项研究将是一个试点项目，以描述这一点 新基因，确定其是否在dHAND和/或 eHAND功能，并确定其基因组结构，为其 评估为负责一种形式的ARVD基因。

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.