人类心脏特异表达基因pygo1的克隆与功能研究

Cloning and Functional Analysis of Human Heart-specific Gene pygo1

心血管疾病已经成为危害人类健康和生命的头号杀手．研究发现，各种心血管疾病与心脏心律失常和心力衰竭有关．wg信号途径直接调控心脏前体细胞的形成和特化过程．pygo基因是近几年在果蝇市新鉴定的一个参与wg信号途径的基因，但pygo是否参与心力衰竭发生的过程尚不得而知．利用RT-PCR的方法，克隆出人类pygo1基因的全长．该基因位于15q21．1，蛋白342～396区域包含一个PHD结构域．亚细胞定位分析表明，pygo1蛋白分布在细胞核中．利用心力衰竭果蝇模型，通过电场对正常和突变基因的成蝇瞬间中断其心脏功能，记录果蝇心衰率的表现，研究pygo的功能．结果表明，果蝇pygo基因突变杂合子的心脏停止跳动和心脏纤维性颤动的比例达32．3％，比对照的高15．6％，表明pygo与心力衰竭的发生有关．

Cardiovascular disease has become the first killer of human life and been threatening people＇s health. Recent investigation suggest that various Cardiovascular disease are related to arrhythmias and cardiomyopathies. Wg singal pathway plays an important role in controlling the specification and differentiation of the cardiac precursor cells. In recent years, pygo has been identified as a gene involving in Wg singal pathway in Drosophila. But it＇s still unknown whether pygo is related to the process of arrhythmias. The author cloned the length of human gene pygol by RT-PCR. The pygol is located on 15q21.1, which contains a PHD domain among 342 - 396 sequence. Subcellular localization experiment showed that pygo distributes in the nucleus. We also use Drosophila as an arrhythmias modle. Applying external electrical pacing, we suspended cardiac function of both gene-mutated Drosophila and control, and recorded the proportion of arrhythmias of Drosophila to study the function ofpygo. The result showed that the proportion of cardiac disease （ including arrest and fibrillation） in pygo hertehrozygote is 32. 3%, 15.6% higher than that of control, indicating that pygo may be involved in arrhythmias.