Zebrafish Pancreas Toxicity Assays

Currently, the mortality rate of mild acute pancreatitis is less than 1%, but the mortality rate of severe pancreatitis can be as high as 30%. Drugs often cause 0.1% to 2% of acute pancreatitis events. Most cases of drug-induced pancreatitis are mild to moderate in severity, but severe and even fatal cases can occur. There is therefore an urgent need for animal models capable of identifying drug-induced pancreatitis during drug development for reducing the risk of drug-induced pancreatitis.

The zebrafish model is now widely integrated into developmental biology and toxicology studies, and the basic structure and function of the pancreas is conserved between zebrafish and mammals. The exocrine compartment of zebrafish secretes enzymes into the digestive tract, and the endocrine compartment produces insulin, glucagon, somatostatin, and ghrelin. Furthermore, zebrafish embryos are transparent and externally fertilized, which allows direct visualization of developing pancreatic structures throughout developmental time. These properties make the zebrafish embryo one of the most suitable models to study pancreatic development and toxicity in vivo, which can be used to elucidate the cellular mechanisms involved in these toxicity.

Fig. 1 Organization of the zebrafish digestive tract and pancreatic islets.

Our Zebrafish Pancreas Toxicity Assays

Our transgenic zebrafish models allow easy visualization of endocrine and exocrine pancreas during organogenesis, such as transgenic zebrafish expressing fluorescent proteins in beta cells. We use these models to test the effects of toxic exposure on pancreatic structure, growth, and expression of related genes, detect sensitive target tissues in live vertebrate embryos in real time, and determine the relationship between toxic exposure and pancreatic defects. We are committed to the coordinated characterization of the pancreatic biochemical, molecular and morphological consequences of toxicological perturbations through our many years of experience with zebrafish.

Our Advantages

Availability of pancreas-specific transgenes
The development of the endocrine and exocrine pancreas can be easily visualized in real time throughout the development of a live embryo
Allows non-invasive observation of toxicity and possible recovery
Rapid identification of toxic drug candidates

References

Prince VE, et al. Zebrafish Pancreas Development and Regeneration: Fishing for Diabetes Therapies. Curr Top Dev Biol. 2017, 124:235-276.
Kinkel MD, et al. On the diabetic menu: zebrafish as a model for pancreas development and function. Bioessays. 2009, 31(2):139-152.
Jacobs HM, et al. Embryonic exposure to Mono(2-ethylhexyl) phthalate (MEHP) disrupts pancreatic organogenesis in zebrafish (Danio rerio). Chemosphere. 2018, 195:498–507.
Sant KE, et al. Embryonic exposures to perfluorooctanesulfonic acid (PFOS) disrupt pancreatic organogenesis in the zebrafish, Danio rerio. Environ Pollut. 2017, 220(Pt B):807-817.

For research use only. Not intended for any clinical use.

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