Zebrafish Polycystic Liver Disease Models

The liver is the largest internal organ and has both exocrine and endocrine functions necessary for survival. Liver failure is one of the leading causes of death and a major health burden worldwide. Polycystic liver disease (PLD) is associated with autosomal dominant polycystic liver disease (ADPLD), autosomal dominant polycystic kidney disease (ADPKD), and autosomal recessive polycystic kidney disease (ARPKD). PLD is manifested by numerous fluid-filled cysts scattered throughout the liver parenchyma, which cause massive enlargement of the liver, compressing adjacent organs and impairing their function. Patients with PLD are at high risk of developing cholangitis, fibrosis, cirrhosis and even cancer.

The zebrafish has become an excellent system for studying liver disease. Zebrafish livers contain the major cell types found in mammalian livers and exhibit similar pathogenic responses to environmental insults and genetic mutations. Zebrafish have been used to model neonatal cholestasis, cholangiopathies such as polycystic liver disease, alcoholic liver disease, and nonalcoholic fatty liver disease. The zebrafish model has several advantages, including relatively easy and economical maintenance, short generation time, external fertilization, production of large numbers of rapidly developing embryos per mating, and development of transparent embryos. Transparency enables the use of fluorescent trackers, and the large number of embryos produced enables rapid screening of variables, including potential therapeutic compounds.

Fig. 1 Morpholinos induced hepatic cyst formation in zebrafish.

Our Zebrafish Polycystic Liver Disease Models

Creative Biogene can provide zebrafish models representative of PLD with unique hepatic and pathogenic features that in many ways resemble human liver pathology. We knocked down sec63, prkcsh, and pkd1a in zebrafish by antisense morpholino oligonucleotides to induce hepatic cyst formation. These models will help study the mechanisms of cyst formation and progressive growth, and evaluate treatment options for inherited cystic diseases. With more than ten years of experience in zebrafish research, our powerful zebrafish research platform can not only be used to conduct detailed developmental genetic analysis, advance your understanding of the etiology of liver disease, but also can be used to select drugs that can inhibit liver cyst formation, to promote the development of new treatments for PLD.

Advantages

• High-throughput gene and drug screening
• Rapidly perform reverse and forward genetic screening
• Track labeled cells in in vivo imaging analysis
• Labeling individual hepatocyte types using a transgenic fluorescent reporter strain, enabling real-time tracking of their morphology and behavior during development and injury

References

1. Tietz Bogert PS, et al. The zebrafish as a model to study polycystic liver disease. Zebrafish. 2013, 10(2):211-217.
2. Pham DH, Zhang C, Yin C. Using zebrafish to model liver diseases-Where do we stand?. Curr Pathobiol Rep. 2017, 5(2):207-221.

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