Transgenic Expression of A Venous Malformation Related Mutation, , Significantly Induces Multiple Malformations of Zebrafish.

A mutation causing arginine-to-tryptophan substitution at residue 849 () is commonly identified in heredofamilial venous malformation. However, there is no model to confirm the pathogenic role of . Humanized plasmid was constructed via PCR-mediated site-directed mutagenesis. After transcription and micro-injection, significantly induces multiple malformations in zebrafish: caudal vein plexus (CVP) defect, eye abnormalities, forebrain formation perturbations, and mandibular malformation. Histologically, these phenotypes accompany aphakia, confused retina plexiform layer, abnormal mandibular cartilage, ectopic myelencephalon proliferation and aberrant location of neurogliocytes. According to qRT-PCR, except for high expression of , the other CVP-related genes , , and are not significantly different from control. also induced upregulation of the signaling pathway. Gene array shows that under the effect of , consistent with high expression of and , high levels of , , and were partly confirmed. This model directly identifies the venous-related pathogenic role of . Under up-regulation of , could be considered a potential reason for venous defects. Moreover, the pathway may perform an important role as a key trigger for head multi-malformations.