条件性敲除APC基因小鼠肠道腺瘤模型的构建  

Construction of Mouse Intestinal Adenoma Model via Conditionally Knocking Out APC from Epithelium

作　　者：廖超男[1] 杨治平[2] 林良武[3] 杨智英 蔡金杏[1] 熊璐[1] 黄河[1] 

机构地区：[1]中南大学基础医学院,中国湖南长沙410013 [2]中南大学湘雅三医院,中国湖南长沙410013 [3]中南大学粉末冶金研究院,中国湖南长沙410013 [4]长沙卫生职业学院,中国湖南长沙410100

出　　处：《生命科学研究》2016年第5期424-428,470,共6页Life Science Research

基　　金：国家自然科学基金项目(NSFC31571241;NSFC31660266);湖南省科技计划项目(2014FJ3146);中南大学教师研究基金(2013-jsjj036);中南大学中央高校基本科研业务费专项资金资助(2013zzts281);长沙市科技计划(K13ZD041-33)

摘　　要：腺瘤性结肠息肉病(adenomatous polyposis coli,APC)基因是家族性腺瘤性息肉病(familial adenomatous polyposis,FAP)的致病基因,APC基因的突变导致小鼠多处产生肿瘤,但肠道条件性敲除APC基因后,小鼠的表型并不清楚。该研究利用Cre-LoxP重组酶系统,在肠道绒毛和隐窝上皮细胞条件性敲除APC基因,并对小鼠表型进行鉴定和分析。将Villin Cre小鼠和APC^(fl/fl)小鼠合笼得到Villin Cre;APC^(fl/+)小鼠;有意思的是后者进一步与APC^(fl/fl)小鼠合笼,却没有得到Villin Cre;APC^(fl/fl)小鼠。进一步解剖Villin Cre;APC^(fl/+)小鼠,发现其自发产生肠道肿瘤,并能携瘤生存,免疫组化显示瘤体组织激活了Wnt信号通路。结果表明成功地构建了小鼠肠道条件性敲除APC基因腺瘤模型,为进一步研究APC基因在肠道发育以及肠道肿瘤的作用提供了优良的工具。The adenomatous polyposis coli （APC） gene has been discovered independently in a hereditary can- cer syndrome termed familial adenomatous polyposis （FAP）. Mutation of A PC can lead to multiple neoplasms in mice, but the phenotype in a mouse with conditional knockout of the APC gene, which genetically re- moves A PC from the intestinal simple epithelium, is not clear. Via Cre-LoxP recombination enzyme system, the APC gene was knocked out in the epithelial cells of the intestinal villi and crypt cells, and the pheno- type was identified and analyzed. When VillinCre was crossed with APCfl/fl, ViUinCre;APCfl/＋ developed in- testinal tumor spontaneously and Wnt signal pathway was activated in these neoplasms. Surprisingly, VillinCre;APCfl/flnever appeared by crossing ViltinCre;APCfl/＋ with APCfl/fl. The results showed that VillinCre; A PCfl/＋ mouse has been generated, which would be a wonderful model for further research of APC gene in intestine development and oncogenesis.

关 键 词：腺瘤性结肠息肉病基因(APC) 条件性基因敲除 小鼠肠道肿瘤模型 Cre-LoxP重组酶系统 

分 类 号：R735.3[医药卫生—肿瘤]