Mutation of rnf213a by TALEN causes abnormal angiogenesis and circulation defects in zebrafish

Abstract

Moyamoya disease (MMD) is characterized by a stenosis at the terminal of the internal carotid artery and an abnormal vascular network at the base of the brain. RNF213 is a susceptibility gene for MMD in East Asians. The role of RNF213 in the etiology of MMD remains unknown. Here we generated rnf213a mutant zebrafish using transcription activator-like effector nuclease (TALEN) technique and described the characteristics of a zebrafish embryonic model of MMD. rnf213a mutant zebrafish developed abnormal angiogenesis in intersegmental vessels and cranial secondary vessels. Endothelial cells exhibited the defects in morphogenesis and formation of vascular tubes despite normal cell to cell contacts under electron microscope. Circulatory disorder was induced by abnormal sprouts in the trunk and head. Reduced circulation in the abnormal vessels was revealed by microangiography. No blood flow permeated across the vessels wall despite the extremely abnormal structure. rnf213a mutant showed lower erythrocyte velocity in dorsal aorta than that in wild-type siblings. In this study, we provided a promising in vivo model for MMD, and this model would aid to understand the function of rnf213a in angiogenesis.

Keywords: Angiogenesis; Circulation; TALEN; Zebrafish; rnf213a.