Generation of a Transgenic Zebrafish Model for Pancreatic Beta Cell Regeneration

Hossein Pourghadamyari; Mohammad Rezaei; Mohsen Basiri; Yaser Tahamtani; Behrouz Asgari; Seyedeh-Nafiseh Hassani; Reza Meshkani; Taghi Golmohammadi; Hossein Baharvand

doi:10.31661/gmj.v8i0.1056

Generation of a Transgenic Zebrafish Model for Pancreatic Beta Cell Regeneration

Galen Med J. 2019 Nov 6:8:e1056. doi: 10.31661/gmj.v8i0.1056. eCollection 2019.

Authors

Hossein Pourghadamyari¹, Mohammad Rezaei², Mohsen Basiri³, Yaser Tahamtani³, Behrouz Asgari³, Seyedeh-Nafiseh Hassani³, Reza Meshkani¹, Taghi Golmohammadi¹, Hossein Baharvand^{3

4}

Affiliations

¹ Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
² Fishery Faculty, Gorgan University of Agriculture Science and Natural Resources, Gorgan, Iran.
³ Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
⁴ Department of Developmental Biology, University of Science and Culture, Tehran, Iran.

Abstract

Background: Diabetes is a major worldwide health problem. It is widely accepted that the beta cell mass decreases in type I diabetes (T1D). Accordingly, beta cell regeneration is a promising approach to increase the beta cell mass in T1D patients. However, the underlying mechanisms of beta cell regeneration have yet to be elucidated. One promising avenue is to create a relevant animal model to explore the underlying molecular and cellular mechanisms of beta cell regeneration. The zebrafish can be considered a model in beta cell regeneration studies because the pancreas structure and gene expression pattern are highly conserved between human and zebrafish.

Materials and methods: In this study, the Tol2 transposase was exploited to generate a Tg(Ins:egfp-nfsB) zebrafish model that expressed a fusion protein composed of enhanced green fluorescent protein (EGFP) and nitroreductase (NTR) under control of the Ins promoter.

Results: Metronidazole (MTZ) treatment of Tg(ins:egfp-nfsB) zebrafish larvae led to selective ablation of beta cells. Proof-of-concept evidence for beta cell regeneration in the transgenic larvae was observed two days after withdrawal of MTZ.

Conclusion: This study suggests that the Tg(ins:egfp-nfsB) zebrafish can be used as a disease model to study beta cell regeneration and elucidate underlying mechanisms during the regeneration process.

Keywords: Diabetes; Genetically Modified Animals; Pancreatic Beta Cells; Regeneration.