WWTX是在Wilm's瘤中新发现的首个定位于X染色体的抑癌基因。目前WTX在全身脏器的生理功能及肿瘤进展中的作用和机制尚太清楚。本课题组在WTX发现之初即开始其肾外功能研究，并发现WTX在多脏器具抑癌基因特性、结直肠是其重要效应器官之一。建立基因敲除动物模型是抑癌基因功能研究的重要手段，也是必经之路。为探讨WTX基因生理功能及其在结直肠癌发生发展中的作用和分子机制，本研究拟应用Cre／loxP系统并结合APCmin/+突变小鼠，建立一组结直肠特异性WTX基因条件性敲除动物模型，比较模型鼠表型、基因型和肿瘤进展情况；分析结直肠特异性基因敲除小鼠自发肿瘤中WTX相关信号通路和miRNAs变化；揭示WTX基因生理功能及基因沉默在结直肠肿瘤发生发展过程中的作用和机制；为WTX相关的肿瘤靶向治疗、药物筛选及肿瘤发生分子机制研究提供新理论、新方法和新靶标。

WTX is a novel X chromosome located tumor suppressor gene which was firstly found in the Wilm's tumor. The functions and mechanism of WTX in normal organs and tumorgenesis are still not clear. We started the WTX gene extra-renal function researchs at the begining of it's report. And we had confirmed that WTX might be a general tumor suppressor and colorectal epithelia were the other one of the most important effectors. Establishing the gene knockout animal model is an important meathod for tumor suppressor gene function research. To explore the functions and mechanism of WTX in normal colorectal tissues and colorectal tumorgenesis, this study will establish the colorectal-specific conditional WTX gene knockout mice models, including colorectal-specific knockout mice (Lgr5cre;WTX-) and combined colorectal-specific knockout and APC min/+ mutant mice (Lgr5cre;WTX-APCmin/+). Then the phenotype, genotype and tumor progressions of these models will be observed. And the changes of WTX related signal pathways and miRNAs will be analyzed in the spontaneous tumors of the WTX colorectal knockout mice. This research will reveal the functions and mechanism of WTX gene silencing in vivo, and provide new clues and models for molecular targeted therapy and drug screening study.