先天性肾脏和尿路畸形（congenital anomalies of the kidney and urinary tract，CAKUT）是造成儿童终末期肾病的主要原因之一。胚胎期肾脏发育异常，尤其是后肾发育异常是导致CAKUT表型发生的基础。基于临床CAKUT病人中Robo2、Gen1复合基因突变的检出，以及预实验中Robo2/Gen1基因双敲小鼠中CAKUT表型的加重，本研究拟利用新型后肾研究工具小鼠Hoxb7/mVnus构建荧光标记ROBO2/GEN1双敲小鼠，动态观察基因突变对输尿管芽萌出、分支的影响；同时通过对双敲小鼠中后肾发育关键分子（GDNF、Gremlin1、BMP4）表达的检测及体外调控（重组蛋白/si-RNA干预）培养胚肾组织中发育关键因子的表达，探索其调控输尿管芽萌出和分支的分子机制，为CAKUT疾病机理提供新的认识。

Congenital anomalies of the kidney and urinary tract are common causes of chronic kidney disease in infants and young children. Embryonic kidney abnormalities, especially metanephros induce CAKUT phenotype occurrence. Based on Robo2, Gen1 complex gene mutation detection in clinical CAKUT patients, as well as preliminary experiments suggest that Robo2 / Gen1 gene double knockout mice show more sever CAKUT phenotype. In this study, we will use Hoxb7 / mVnus mice to construct fluorescence marked ROBO2 / GEN1 double knockout mice, dynamically observe it's impact on the process of ureteric bud eruption and branching, and through systematically research on the key regulatory molecules (GDNF, Gremlin1, BMP4, etc.), explore the molecular mechanism of ureteric bud eruption, and provide a new understanding of developmental biology and disease.