CLONING OF A POTENTIAL REGULATOR OF THE DHAND FACTOR

描述(改编自申请人的描述)：描述 引导心室成熟的分子信号级联反应是 对我们理解正常的心脏发育至关重要，并可能使 影响先天性心脏缺陷病因的鉴定 心脏结构或功能。脑室发育异常 在整个前和前两年都有很高的发病率和死亡率 产后期。这个实验室的目标是研究 通过以下途径引导右室和左室发育的信号级联 研究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。 控制左右方向的不同调控通路中的元件 (EHAND)脑室发育。在我们实验室的初步研究中， 在酵母双杂交系统中发现了一种新的与DHAND相互作用的蛋白 模特。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。它已经被本地化到一个地区 这与遗传性脑室发育异常有关 致心律失常右室的结构和电生理功能 异型增生(ARVD)。这项研究将是描述这一特征的一个试点项目 新基因，确定它是否在DHAND和/或 EHAND的功能，并确定其基因组结构，为其 评估为导致一种形式的ARVD的基因。

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.