KRAS条件突变小鼠肺腺癌模型的构建  

Construction of a KRAS conditional mutation mouse lung adenocarcinoma model

作　　者：陈勇 吴俊 汪梦梦 王霄霖 束余声 CHEN Yong;WU Jun;WANG Mengmeng;WANG Xiaolin;SHU Yusheng(Dalian Medical University,Liaoning Dalian 116004,China;Department of Thoracic Surgery,Sichuan Cancer Hospital&Institute,Sichuan Cancer Center,Sichuan Chengdu 610041,China;Yangzhou University,Jiangsu Yangzhou 225009,China;Department of Thoracic Surgery,Subei People's Hospital,Jiangsu Yangzhou 225001,China)

机构地区：[1]大连医科大学,辽宁大连116004 [2]四川省肿瘤临床医学研究中心,四川省癌症防治中心,四川省肿瘤医院胸外科,四川成都610041 [3]扬州大学,江苏扬州225009 [4]苏北人民医院胸外科,江苏扬州225001

出　　处：《现代肿瘤医学》2024年第18期3420-3426,共7页Journal of Modern Oncology

基　　金：江苏省卫生健康委员会老年健康科研课题项目(编号:LKZ2022019);江苏省扬州市科技局社会发展项目(编号:YZ2023084);江苏省扬州市创新能力建设计划项目(编号:YZ2022168)。

摘　　要：目的:旨在建立基因编辑的小鼠肺腺癌模型,探究肺腺癌在不同时间点的发展情况以及不同性别小鼠成瘤的差异。方法:利用KRAS^(LSL-G12D)条件突变的C57BL/6J小鼠,通过繁衍扩增鉴定后,采用气管插管递送载有环化重组酶的腺病毒(Ad-Cre)到小鼠肺组织,诱导KRAS基因的突变表达,从而引发肺部肿瘤。分别在感染后1~8个月收集小鼠全肺,石蜡包埋切片后进行HE染色,比较不同时间段及不同性别小鼠肺腺癌成瘤情况。结果:随着递送Ad-Cre的时间增加,小鼠肺腺癌成瘤比例增加,在递送Ad-Cre后6个月成瘤率达100%,同时成瘤的数量和大小也随着时间延长而增长。在成瘤的小鼠肺腺癌中,除感染Ad-Cre后1个月的病变表现为不典型增生外,在感染2个月后的成瘤肿块中均形成了浸润性肺腺癌。此外,不同性别的小鼠在肺腺癌成瘤的表现上无明显差异。结论:KRAS^(LSL-G12D)条件突变小鼠通过气管插管递送Ad-Cre能有效构建肺腺癌模型,且不同性别小鼠肺腺癌的成瘤率没有显著差异。Objective:To establish a genetically engineered a mouse model of lung adenocarcinomaand investigate the development of lung adenocarcinoma at different time points,as well as differences in tumor formation between male and female mice.Methods:C57BL/6J mice with KRAS^(LSL-G12D)conditional mutations were used.After breeding and amplification,adenovirus carrying Cre recombinase(Ad-Cre)was delivered to the lung tissue of mice via endotracheal intubation to induce mutation of the KRAS gene,thereby initiating lung tumor formation.Whole lung tissues were collected at 1~8 months post-infection,embedded in paraffin,and subjected to HE staining to compare lung adenocarcinoma tumor formation at different time points and between different sexes.Results:With increasing delivery time of Ad-Cre,the proportion of lung tumors in mice increased,reaching 100%tumor formation rate at 6 months,with tumor number and size increasing over time.In mice with lung adenocarcinoma tumors,except for atypical hyperplasia observed at 1 month post-infection with Ad-Cre,invasive lung adenocarcinomas were formed after 2 months.Additionally,there was no significant difference in lung adenocarcinoma tumor formation efficiency between female and male mice.Conclusion:KRAS^(LSL-G12D)conditional mutation mice can effectively establish a lung adenocarcinoma model through endotracheal intubation delivery of Ad-Cre,with no significant effect of gender on lung adenocarcinoma tumor formation rate.

关 键 词：肺腺癌 小鼠模型 KRAS 环化重组酶 

分 类 号：R734.2[医药卫生—肿瘤]