Generation of a Transgenic Zebrafish Model for Pancreatic Beta Cell Regeneration.

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() zebrafish model that expressed a fusion protein composed of enhanced green fluorescent protein (EGFP) and nitroreductase (NTR) under control of the promoter.

Results: Metronidazole (MTZ) treatment of Tg() 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() zebrafish can be used as a disease model to study beta cell regeneration and elucidate underlying mechanisms during the regeneration process.