Genetically engineered mouse model of HPV16 E6-E7 with vaginal-cervical intraepithelial neoplasia and decreased immunity

作者全名：Du, Xiurong; Xin, Zhou; Li, Deng; Wang, Yanzhou; Ling, Kaijian; Liang, Zhiqing

作者地址：[Du, Xiurong; Xin, Zhou; Liang, Zhiqing] Army Med Univ, Dept Pathophysiol, Chongqing 400038, Peoples R China; [Du, Xiurong; Xin, Zhou; Li, Deng; Wang, Yanzhou; Ling, Kaijian; Liang, Zhiqing] Third Mil Med Univ, Army Med Univ, Southwest Hosp, Dept Obstet & Gynecol,Affiliated Hosp 1, Chongqing 400038, Peoples R China; [Liang, Zhiqing] Army Med Univ, Chongqing 400038, Peoples R China

通信作者：Wang, YZ; Ling, KJ; Liang, ZQ (通讯作者)，Third Mil Med Univ, Army Med Univ, Southwest Hosp, Dept Obstet & Gynecol,Affiliated Hosp 1, Chongqing 400038, Peoples R China.; Liang, ZQ (通讯作者)，Army Med Univ, Chongqing 400038, Peoples R China.

来源：HELIYON

ESI学科分类：　

WOS号：WOS:001240297700001

JCR分区：Q1

影响因子：3.4

年份：2024

卷号：10

期号：10

开始页：　

结束页：　

文献类型：Article

关键词：Genetically engineered mice; HPV16-E6-E7; CRISPR/Cas9; C57BL/6 N mice; Precancerous lesions

摘要：Objective: To construct models of high-risk human papillomavirus (HPV) infection with precancerous lesions or cervical cancer and explore the immune function. Methods: Using CRISPR/Cas9, the expression vector HPV16-E6-E7-Rosa26 was microinjected into fertilized eggs of C57BL/6 N mice using homologous recombination, and the F0 generation was obtained for reproduction. Then, the formation of precancerous lesions was promoted via intramuscular injection of estradiol. Presence of precancerous cervical-vaginal intraepithelial lesions, Ki67 and p16 expression levels, and CD8+ T cell proportions in the spleen were evaluated. Results: Two F0 generation mice exhibited correct the homologous recombination. Seven positive mice were identified in the F1 generation. After breeding and mating, 25 homozygous and 11 heterozygous HPV16-E6-E7-engineered mice were obtained from the F2 generation. After estradiol benzoate treatment, the cervical-vaginal epithelium appeared as precancerous lesions with positive Ki67 and p16 expression. The percentage of CD8+ T cells decreased. Conclusion: HPV16-E6-E7-Rosa26 induced low immune function in mice, and provides a good model for the basic research of the mechanisms of action of HPV infection-associated precancerous lesions or cervical cancer.

基金机构：National Key Technology R & D Program of China [2019YFC1005200]

基金资助正文：This study was approved by the National Key Technology R & D Program of China, with the approval number: [2019YFC1005200