条件性基因敲除诱导剂他莫昔芬对小鼠肠道微生物群组成的影响  

Effects of Conditional Gene Knockout Inducer Tamoxifen on the Composition of Mice Gut Microbiota

作　　者：余丹妮 孙璘 YU Danni;SUN Lin(Institute of Developmental Biology and Molecular Medicine,School of Life Sciences,Fudan University,Shanghai 200438,China)

机构地区：[1]复旦大学生命科学学院发育生物学研究所,上海200438

出　　处：《复旦学报（自然科学版）》2024年第1期68-76,共9页Journal of Fudan University：Natural Science

基　　金：国家重点研发计划(2019YFA0802303);上海市教育委员会科研创新计划(2019-01-07-00-07-E00041)。

摘　　要：他莫昔芬(Tamoxifen)作为一种选择性雌激素受体调节剂,在临床上应用于治疗乳腺癌,在生物遗传学领域研究中充当诱导型Cre-loxP条件性基因敲除系统的时空开关。肠道微生物与宿主基因紧密相连,与宿主肠道吸收、代谢、发育性疾病、肿瘤密切相关,利用他莫昔芬诱导特定基因敲除已成为探究微生物与宿主基因互作的主要研究方式。已有研究表明他莫昔芬引发雌激素受体介导的毒性,干扰宿主生物学功能,少有研究报道他莫昔芬本身是否对小鼠肠道微生物群的稳定性造成影响,本研究通过给野生型C57BL/6J小鼠注射他莫昔芬模拟条件性基因敲除以研究其影响及机制。研究结果发现,注射他莫昔芬组与对照组相比,小鼠体重、肠道组织结构与形态及肠道屏障功能无明显差异,但他莫昔芬对小鼠粪便和盲肠内容物中的微生物丰度产生影响。这些结果提示使用他莫昔芬诱导小鼠条件性基因敲除时需要注意肠道菌群改变带来的生理和病理表型,从而减少他莫昔芬带来的干扰。Tamoxifen is a selective estrogen receptor modulator.In addition to being used in treatment for breast cancer,it also acts as a spatial-temporal switch in the inducible Cre-loxP gene knockout system.Gut microbiota is closely related to physiological conditions of the hosts,such as intestinal absorption,metabolism,developmental diseases and cancer.Tamoxifen-induced specific gene knockout has become a popular method to explore the interaction between microbiota and host genes.Tamoxifen injection can cause estrogen receptor-mediated toxicity,which may interfere the physiological status of the hosts.However,whether tamoxifen injection has an impact on the gut microbiota stability in mice remains unclear.In this study,we injected tamoxifen to C57BL/6J wild type mice following the protocol commonly used for gene conditional knockout and explored the effect of tamoxifen injection.The results showed that there was no significant difference in body weight,intestinal structure and morphology as well as the intestinal barrier between tamoxifen-injected group and control group.However,tamoxifen administration did have an impact on the microbial abundance in the fecal and cecal contents of the mice.Our work indicates that when using tamoxifen to induce conditional gene knockout in mice,it is necessary to take into account the potential impact of tamoxifen on the gut microbiota and minimize any potential interference that may arise.

关 键 词：他莫昔芬 Cre-loxP条件性基因敲除系统 肠道微生物群 

分 类 号：Q3-3[生物学—遗传学]