常染色体显性多囊肾病是一种最常见的单基因遗传性肾病，占肾衰竭病因的第4位。初级纤毛是肾小管上皮细胞的一种细胞器，在多囊肾病的发病机制中起着共同通路的作用。本项目申请者成功建立了I型多囊肾病基因敲入小鼠模型（PNAS，2007），前期研究发现纯合子小鼠双侧肾脏囊肿形成，通过蛋白组学的研究获得了多个囊肿相关差异表达蛋白。为进一步深入研究差异表达蛋白在囊肿形成中的作用、寻找治疗靶标，本项目拟在细胞模型、小鼠模型和人多囊肾病肾脏组织标本上，运用免疫印迹、免疫荧光双染色、激光共聚焦、电子显微镜等方法研究前期获得的囊肿相关差异表达蛋白在细胞和初级纤毛上的表达、分布，从中筛选出1-2种囊肿相关差异表达蛋白，通过上调和下调差异蛋白的表达观察对初级纤毛的结构和蛋白分布的影响，并研究其发生机制，为明确囊肿相关差异蛋白在细胞和初级纤毛中的分布及表达差异，探索多囊肾病的发病机制、寻找治疗靶标奠定一定的理论基础。

Autosomal dominant polycystic kidney disease （ADPKD） is the most common monogenic renal disease, and it is the forth cause of end-stage renal disease. Primary cilia is an organ of tubular epithelial cell of kidney . It is the common pathway of the pathogenesis of autosomal dominant polycystic kidney disease. The applicant of this project successfully founded Pkd1 gene knock-in mouse model　（PNAS,2007）. The former study results indicated that renal cysts are formed in the homozygote mice and several different expression proteins were found by the proteomics study. To further explore the role of the different expression protein on kidney cyst formation, the applicant plans to study the expression and distribution of the cyst-related different expression proteins on the epithelial cell and primary cilia using the cell model, mouse model and human kidney cyst lining epithelial cells by Western Blot, double immunofluorescence staining,electric microscope, etc. Screening 1-2 cyst-related different expression proteins form them, and observing the effect on the structure and protein distribution of primary cilia through upregulation and downregulation of the different expression protein. Also study the pathogenesis to the further. More information about the pathogenesis of PKD and therapy target may be got from this project.