Prox1-CreERT2介导的受体酪氨酸激酶Tie2 敲除对小鼠心脏发育的影响
首发时间:2019-03-22
摘要:目的:利用表达可诱导Cre重组酶的Prox1-CreERT2转基因小鼠,分析其介导的受体酪氨酸激酶Tie2基因敲除对心脏发育的影响。方法:转录因子PROX1在淋巴管、心脏、肝等多种组织中有表达;TIE2是调控心血管发育的关键因子。本课题组先前的研究发现,在胚胎中期利用Prox1-CreERT2转基因小鼠介导Tie2基因敲除导致小鼠发生水肿。为进一步探究该表型是否与心脏发育有关,本研究利用Prox1-CreERT2转基因小鼠、靶向Tie2的条件性基因敲除小鼠,并结合ROSA26-mT/mG报告基因小鼠模型,研究Tie2敲除对于小鼠心脏与心血管发育的影响。结果:表型分析表明,Prox1-CreERT2可介导ROSA26-mT/mG的报告基因(mG,即细胞膜GFP)在淋巴管内皮细胞以及心肌细胞表达。在Tie2基因敲除的小鼠模型中,小鼠心脏发育包括心房和心室的结构、以及心血管的网络结构无明显异常;利用免疫组化分析血管α-SMA、以及血液红细胞的结果表明,在PROX1阳性细胞诱导敲除Tie2基因对血管的渗漏性无明显影响。结论:胚胎中后期诱导敲除Tie2对小鼠心脏四个腔室的形成、心血管生长与结构无明显影响;关于Tie2缺失导致的水肿是否与淋巴管发育有关尚待深入研究。
关键词: Tie2条件性基因敲除 Prox1 诱导型Cre重组酶转基因小鼠 心脏发育 心血管生成 心肌层
For information in English, please click here
Effect of Prox1-CreERT2 mediated receptor tyrosine kinase Tie2 knockout on cardiac development in mice
Abstract:Objective: To investigate the effects of Prox1-CreERT2 transgenic mice, which express inducible Cre recombinase, mediated receptor tyrosine kinase Tie2 knockout on cardiac development. Methods: Transcription factor PROX1 is expressed in various tissues such as lymphatic vessels, heart, and liver; TIE2 is a key regulatory factor for cardiovascular development. Previous studies by our group have shown that subcutaneous edema occurred in mice with Tie2 knockout mediated by Prox1-CreERT2 transgenic mice at middle embryonic stage. To further explore whether this phenotype is related to heart development, this study used Prox1-CreERT2 transgenic mice, conditional gene knockout mice targeting Tie2, plus with ROSA26-mT/mG reporter gene mouse model, to explore the effects of Tie2 knockout on heart and cardiovascular development in mice. Results: Phenotypic analysis showed that Prox1-CreERT2 could mediate the expression of ROSA26-mT/mG reporter gene (mG, membrane-localized GFP) in lymphatic endothelial cells and cardiomyocytes. In Tie2 gene knockout mouse model, there were no significant abnormalities in heart development, including the structure of the atrium and ventricle, as well as cardiovascular network; immunohistochemical analysiswas used to analyze vascular α-SMA and red blood cells, it showed that induced Tie2 gene knockout in PROX1 positive cells has no significant effect on the permeability of blood vessels. Conclusion: There was no significant effect on the formation of four chambers in the heart, cardiovascular growth and structure by induced knockout of Tie2 in the middle and late embryonic stage; whether edema caused by Tie2 deficiency is related to lymphatic development remains to be further studied.
Keywords: Tie2 conditional gene knockout Prox1 Inducible Cre recombinase transgenic mice Cardiac development Cardiovascular generation Myocardium
引用
No.****
动态公开评议
共计0人参与
勘误表
Prox1-CreERT2介导的受体酪氨酸激酶Tie2 敲除对小鼠心脏发育的影响
评论
全部评论0/1000