Six1/Eya1 转录复合物在泌尿生殖道发育中的作用及其机制

项目名称： Six1/Eya1 转录复合物在泌尿生殖道发育中的作用及其机制

项目编号： No.31271535

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 孙晔

作者单位： 温州医科大学

项目金额： 70万元

中文摘要： 泌尿生殖道畸形是临床最常见的严重危害儿童健康的先天性疾病之一，近年来其发病率逐年上升,原因不明。目前，人们对泌尿生殖道畸形的致病机制尚不清楚，在前期研究中，我们发现缺失Six1 和Eya1 基因的小鼠胚胎出现泌尿生殖道形态异常，与人类泌尿生殖道畸形极为相似。我们推测泌尿生殖道的发育与Six1/Eya1 转录复合物调节下游有关基因转录翻译有关，并需要TGF?/Smad4 信号转导分子的参与。我们拟采用Six1 和Eya1 双基因敲除小鼠模型，运用Cre/loxP 位点特异性DNA 重组策略、RNA 原位杂交、X-gal 染色、BrdU标记、iUTC 等手段对上述假设予以验证，探讨Six1/Eya1 调控泌尿生殖道发育的相关机制，为泌尿生殖道畸形的早期基因诊断和治疗提供新的靶点。

中文关键词： 泌尿生殖道发育；Six1 基因；Eya1基因；发育机制；基因突变

英文摘要： As one of congenital diseases, genitourinary tract malformation has now been increasing in recent years. The pathogenic mechanism of genitourinary tract malformation is still unclear. In previous studies, we found that the deficiency of Six1 and Eya1 gene in mouse embryo resulted in the genitourinary tract morphologic abnormality, which is similar to the human genitourinary tract malformation. Thus, we hypothesize that Six1/Eya1 transcriptional complex-regulated downstream gene transcription and translation may be involved in the development of genitourinary tract, and TGF-beta/Smad4 signaling transduction may be also involved. In this project, we try to demonstrate the related mechanism of Six1/Eya1-regulated genitourinary tract development by a series of experiments and models, including Six1-/- and Eya1-/- mice, Cre/lox P sit specific DNA recombination, RNA in situ hybridization, X-gal staining, BrdU label, and iUTC. These studies will provide us new targets for the early genetic diagnosis and treatment of genitourinary tract malformation.

英文关键词： genitourinary development；Six1；Eya1；developmental mechanisms；gene mutation