关键词: 静脉畸形, 尾静脉丛, 斑马鱼, Egfl7

Abstract: PURPOSE: To explore the role of TIE2-R849W, a mutation related to hereditary venous malformations, via establishing a novel zebrafish model. METHODS: Through the designment and synthesis of TIE2-R849W expression plasmid, translated mRNA was microinjected into fli1a: EGFP fertilized eggs, which were used to establish a TIE2-R849W over-expression model. Under fluorescence microscope, the developmental change of caudal vein plexus (CVP) was recorded and quantitatively compared. Using RNA extracted from zebrafish, target genes were tested by real-time quantitative PCR (qRT-PCR). The existing gene chip was analyzed to further verify the results. Statistical analysis was performed with GraphPad Prism 5. RESULTS: Based on observed phenotypes of TIE2-R849W over-expression zebrafish, TIE2-R849W significantly affected the development of the caudal venous plexus, which displayed a significant decrease in the number and area of sinus. According to the results of qRT-PCR, upregulation of pik3r2 and foxo1b could be induced by TIE2-R894W over-expression. At the same time, except for significantly up-regulated egfl7, expression of nr2f2, nr2f1a and s1pr1 had no significant difference from the control. In contrast to in vitro chip analysis, tie2, pik3r2, foxo1b and egfl7 showed consistent high expression in individual mutant group. CONCLUSIONS: TIE2-R849W associated with hereditary venous malformations could induce abnormal development of zebrafish CVP, which implies a possible relationship between VM and egfl7.

Key words: Venous malformations, Caudal vein plexus, Zebrafish, Egfl7