【作者】 罗开梅；

【导师】 吴秀山； 袁婺洲；

【作者基本信息】 湖南师范大学 ， 生物化学及分子生物学， 2003， 硕士

【摘要】 基因的正确表达和细胞的正确生长对所有器官的发育和生存起关键作用，基因表达和细胞生长调控的异常将导致一系列疾病的发生，这其中包括先天性心脏病和癌症。心脏发育是一个非常复杂的过程，它需要精确的基因表达调控。为了鉴定控制心脏发育和疾病发生的新基因，本研究从心脏cDNA文库克隆了5个新基因，ZNF382，ZNF359，ZFP28，ZNF323和Irx1，它们分别位于染色体19q13.13，16q22，19q13.43，6p22.3-p22.1和5p15.3位点。前面4个基因属于C2H2-型锌指蛋白家族，Irx1属IRX蛋白家族，它们都是转录因子，研究表明这两个家族蛋白都参与心脏的发育或疾病发生过程。Northern杂交和胚胎原位抗体染色结果表明ZNF382主要在成体心脏组织表达，ZNF382可能在心脏发育和心脏功能的发挥中起重要作用，相对比，Irx1 mRNA强烈在肾脏，脑和肺组织表达，人类的Irx1基因是否像小鼠和鸡的Irx1基因一样，也参与心脏的发育还需要做进一步的研究。不同的基因在心脏发育阶段中，其表达水平有着时空上的变化，因此，有必要从mRNA和蛋白质水平上研究这5个人类新基因在不同胚胎发育时期的表达变化情况，本研究从mRNA水平上研究了这5个新基因在胚胎时期和成体的表达模式。更多还原

【Abstract】 Proper gene expression and cell growth are critical for the development and survival of all organisms, and defect in their regulation may contribute to a variety of diseases including congenital heart disease (CHD) and cancer. Cardiogenesis is a very complex process that requires precise regulation of gene expression. With the aim of identifying novel genes involved in human heart development and diseases, five novel genes, ZNF382, ZNF359 , ZFP28, ZNF323 and Irx1, were isolated from heart cDNA library. They are mapped to chromosome 19ql3.13, 19ql3.13, 16q22, 19ql3.43, 6p22.3-p22.1 and 5pl5.3, respectively. The former four genes were belonged to Krupple-type Zinc Finger family and Irxl was belonged to Iroquois homeobox family. Both of the families are transcription factors. It was shown that the two family proteins are involved in the cardiogenesis process or cardiac disease. Northern blot analysis and whole-embryo antibody staining indicate that ZNF382 expression is restricted largely to heart tissue suggesting a potential role in heart development and function. In contrast, Irxl mRNA was expressed strongly in kidney, brain, and lung. Whether hIrx1 is involved in heart development like mIrxl and cIrxl remains to be investigated. Different genes (and their protein products) experience changes in their spatio-temporal distribution and level of expression during heart development. Therefore, it is necessary to understand these five genes expression on mRNA and protein levels at different embryonic stages. This study showed the expression pattern of the five novel human genes at mRNA level from embryonic stages to adult.更多还原