Pkhd1基因的缺失可促进Apc^Min/＋小鼠肠道肿瘤的发展演进  

Loss of Pkhd1 promotes intestinal tumorigenesis in ApcMin/＋ mice

作　　者：李维[1] 李奥[1] 李渊[1] 马玉洁[1] 丁镇伟[1] 张宏图[2] 吴冠青[1] 

机构地区：[1]北京协和医学院中国医学科学院肿瘤医院肿瘤临床实验中心分子肿瘤学国家重点实验室,100021 [2]北京协和医学院中国医学科学院肿瘤医院病理科,100021

出　　处：《国际遗传学杂志》2015年第2期64-70,共7页International Journal of Genetics

基　　金：科技部973子课题（2012CB517700）;国家自然科学基金（81072688、81173114、81473282）

摘　　要：目的 确定人类常染色体隐性遗传性多囊肾病（ARPKD）致病基因Pkhd1在ApcMin/小鼠肠道肿瘤发生中的作用.方法 Pkhd1基因敲除小鼠模型（Pkhd1-/-）与肠道肿瘤模型Apc^Min/＋小鼠杂交后,比较不同月龄（1、3、6月）单一Apc^Min/＋小鼠与缺失Pkhd1的ApcMin/＋小鼠（Pkhd1-/-;Apc^Min）肠道肿瘤的数目及大小,并观察其肠道肿瘤组织病理的变化.结果 与单一的Apc^Min/＋小鼠相比,Pkhd1-/-;Apc^Min/＋小鼠在1月龄时,肠道肿瘤数目及大小均无显著差异.但该小鼠在3月龄和6月龄时肠道肿瘤数目及大小均显著增加（P=0.017、P=0.022）.此外,在6月龄时,Pkhd1-/-;Apc^Min/＋小鼠病理表型有向恶性转化的明显趋势.结论 具有Pkhd1缺失的Apc ^Min/＋小鼠与单一的ApcMin/小鼠相比能够显著促进肠道肿瘤的发生和发展,并具有促进其肿瘤恶性转化的趋势.Objective To investigate the role of Pkhd1,an ARPKD casual gene,in intestinal tumorigenesis of Apc^Min/＋ mice.Methods ApcMin/＋ mice were crossed with Pkhd1 knockout mice （Pkhd1-/-） to produce compound Pkhd1-/-; Apc^Min/＋ mice.The tumorigenic susceptibility between Pkhd1-/-; Apc^Min/＋ and Apc^Min/＋ mice was compared.The number,size and pathology of tumors were analyzed at the age of 1,3,and 6 months.Results There was no statistical difference in tumor number and size between 1 month-old Apc^Min/＋ and Pkhd1-/-;Apc^Min/＋ mice.However,the number and size of the intestinal tumors in 3 and 6 month-old Pkhd1-/-; Apc^Min/＋ mice were significantly larger than that of Apc^Min/＋ mice respectively （P =0.017,P =0.022）.In addition,compared to 6 month-old Apc^Min/＋ mice,more malignant transformation was also pathologically observed in the age-matched Pkhd1-/-;Apc^Min/＋ mice.Conclusion Loss of Pkhd1 likely promotes the intestinal tumorigenesis and tumor malignant transformation in Apc^Min/＋ mice.

关 键 词：肠道肿瘤 Apc^Min/+小鼠 常染色体隐性遗传性多囊肾病 Pkhd1 

分 类 号：R730.2[医药卫生—肿瘤]