Full Text | PDF

Share on tweeters Share on facebook Share on linkedin Share on googleplus

Int J Med Sci 2018; 15(4):385-394. doi:10.7150/ijms.23054 This issue Cite

Research Paper

Transgenic Expression of A Venous Malformation Related Mutation, TIE2-R849W, Significantly Induces Multiple Malformations of Zebrafish

Zhong Du, Hai-Long Ma, Zhi-Yuan Zhang, Jia-Wei Zheng, Yan-An Wang✉

Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, PR China.

✉ Corresponding author: Yan-An Wang, (Email: wangyan_ancom)

Citation:
Du Z, Ma HL, Zhang ZY, Zheng JW, Wang YA. Transgenic Expression of A Venous Malformation Related Mutation, TIE2-R849W, Significantly Induces Multiple Malformations of Zebrafish. Int J Med Sci 2018; 15(4):385-394. doi:10.7150/ijms.23054. https://www.medsci.org/v15p0385.htm
Other styles

File import instruction

Abstract

A TIE2 mutation causing arginine-to-tryptophan substitution at residue 849 (TIE2-R849W) is commonly identified in heredofamilial venous malformation. However, there is no in vivo model to confirm the pathogenic role of TIE2-R849W. Humanized TIE2-R849W plasmid was constructed via PCR-mediated site-directed mutagenesis. After transcription and micro-injection, TIE2-R849W 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 egfl7, the other CVP-related genes cd146, nr2f1a, and s1pr1 are not significantly different from control. TIE2-R849W also induced upregulation of the wnt signaling pathway. Gene array in vitro shows that under the effect of TIE2-R849W, consistent with high expression of pik3 and foxo1, high levels of egfl7, wnt9a, lrp5 and dkk1 were partly confirmed. This in vivo model directly identifies the venous-related pathogenic role of TIE2-R849W. Under up-regulation of TIE2-R849W, egfl7 could be considered a potential reason for venous defects. Moreover, the wnt pathway may perform an important role as a key trigger for head multi-malformations.

Keywords: TIE2-R849W, Venous malformation, Zebrafish, Developmental malformation, Egfl7, Wnt

Citation styles

APA
Du, Z., Ma, H.L., Zhang, Z.Y., Zheng, J.W., Wang, Y.A. (2018). Transgenic Expression of A Venous Malformation Related Mutation, TIE2-R849W, Significantly Induces Multiple Malformations of Zebrafish. International Journal of Medical Sciences, 15(4), 385-394. https://doi.org/10.7150/ijms.23054.

ACS
Du, Z.; Ma, H.L.; Zhang, Z.Y.; Zheng, J.W.; Wang, Y.A. Transgenic Expression of A Venous Malformation Related Mutation, TIE2-R849W, Significantly Induces Multiple Malformations of Zebrafish. Int. J. Med. Sci. 2018, 15 (4), 385-394. DOI: 10.7150/ijms.23054.

NLM
Du Z, Ma HL, Zhang ZY, Zheng JW, Wang YA. Transgenic Expression of A Venous Malformation Related Mutation, TIE2-R849W, Significantly Induces Multiple Malformations of Zebrafish. Int J Med Sci 2018; 15(4):385-394. doi:10.7150/ijms.23054. https://www.medsci.org/v15p0385.htm

CSE
Du Z, Ma HL, Zhang ZY, Zheng JW, Wang YA. 2018. Transgenic Expression of A Venous Malformation Related Mutation, TIE2-R849W, Significantly Induces Multiple Malformations of Zebrafish. Int J Med Sci. 15(4):385-394.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image

©2024 Ivyspring International Publisher. Terms of use