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  • 所在单位:生命科学学院
  • 学历:博士研究生毕业
  • 性别:
  • 学位:博士
  • 职称:教授
  • 毕业院校:新加坡国立大学
  • 学科:生物化学与分子生物学
    发育生物学
论文成果
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Generation and Application of the Zebrafish heg1 Mutant as a Cardiovascular Disease Model.
  • 影响因子:4.634
  • DOI码:10.3390/biom10111542.
  • 发表刊物:Biomolecules
  • 关键字:CRISPR/Cas9; Traditional Chinese Medicine (TCM); cardiovascular disease (CVD); dilated cardiomyopathy (DCM); drug screening; heg1; thrombosis; zebrafish model.
  • 摘要:Cardiovascular disease (CVD) is the leading cause of global mortality, which has caused a huge burden on the quality of human life. Therefore, experimental animal models of CVD have become essential tools for analyzing the pathogenesis, developing drug screening, and testing potential therapeutic strategies. In recent decades, zebrafish has entered the field of CVD as an important model organism. HEG1, a heart development protein with EGF like domains 1, plays important roles in the development of vertebrate cardiovascular system. Loss of HEG1 will affect the stabilization of vascular endothelial cell connection and eventually lead to dilated cardiomyopathy (DCM). Here, we generated a heg1-specific knockout zebrafish line using CRISPR/Cas9 technology. Zebrafish heg1 mutant demonstrated severe cardiovascular malformations, including atrial ventricular enlargement, heart rate slowing, venous thrombosis and slow blood flow, which were similar to human heart failure and thrombosis phenotype. In addition, the expression of zebrafish cardiac and vascular markers was abnormal in heg1 mutants. In order to apply zebrafish heg1 mutant in cardiovascular drug screening, four Traditional Chinese Medicine (TCM) herbs and three Chinese herbal monomers were used to treat heg1 mutant. The pericardial area, the distance between sinus venosus and bulbus arteriosus (SV-BA), heart rate, red blood cells (RBCs) accumulation in posterior cardinal vein (PCV), and blood circulation in the tail vein were measured to evaluate the therapeutic effects of those drugs on DCM and thrombosis. Here, a new zebrafish model of DCM and thrombosis was established, which was verified to be suitable for drug screening of cardiovascular diseases. It provided an alternative method for traditional in vitro screening, and produced potential clinical related drugs in a rapid and cost-effective way.
  • 备注:大类:生物 2区 小类:生化与分子生物学 2区
  • 论文类型:期刊论文
  • 学科门类:理学
  • 一级学科:生物学
  • 文献类型:J
  • 卷号:10
  • 期号:11
  • 页面范围:1542
  • 是否译文:
  • 发表时间:2020-11-12
  • 收录刊物:SCI