Zebrafish Glomerulopathy Models

Glomerular disease is the result of diseases that affect specific parts of the kidneys (called glomeruli), and the incidence is increasing. Animal models help to better understand the pathophysiology behind various kidney diseases and screen for therapeutic compounds.

The zebrafish (Danio rerio) is an excellent surrogate for mammalian models and a powerful genetic experimental approach to invertebrates to answer questions about vertebrate development and disease. Multiple studies have demonstrated that the zebrafish is an applicable and versatile experimental system, mainly due to the simplicity of its pronephros, which contains two nephrons with glomerular filtration and tubular filtration processing, in contrast to mammalian nephrons. Has conserved structural and physiological aspects. Given its high genetic and renal similarity to humans, zebrafish have been used to study different kidney diseases, such as focal segmental glomerulosclerosis, polycystic kidney disease, diabetic nephropathy, and kidney cancer.

Fig.1 Evaluation of glomerular function in zebrafish.

Our Zebrafish Glomerulopathy Models

Our zebrafish model recapitulates human hereditary glomerulopathy, a variety of podocyte diseases that often manifest clinically as steroid-resistant nephrotic syndrome due to loss of podocyte foot processes. Among them, a wt1a knockout zebrafish model exhibited defective podocyte development, leading to glomerular damage and nephropathy. The zebrafish nphs2 morphants model exhibits glomerular hypoplasia with pericardial edema and ultrastructural glomerular damage to the filtration barrier. We visualize disruption of the glomerular filtration barrier by ultrastructural techniques such as super-resolution or electron microscopy that are not compatible with large chemical screens. In addition, we generated transgenic zebrafish that express GFP (green fluorescent protein)-tagged vitamin D-binding protein, which acts as a tracer for proteinuria and supports high-content and high-throughput screening.

Advantages

• Phenotypic screening for high content and high throughput experiments
• Availability and ease of use of gene editing technologies
• Function to rapidly assess glomerular filtration and barrier integrity
• Real-time observation of the disease process

Creative Biogene is dedicated to providing new insights into the pathogenesis of AD, helping you better understand the pathophysiology behind various kidney diseases and screen for therapeutic compounds. If you would like to learn more about zebrafish models, please feel free to contact us.

References

1. Gehrig J, Pandey G, Westhoff JH. Zebrafish as a Model for Drug Screening in Genetic Kidney Diseases. Front Pediatr. 2018, 6:183.
2. Outtandy P, et al. Zebrafish as a model for kidney function and disease. Pediatr Nephrol. 2019, 34(5):751-762.
3. Elmonem MA, et al. Genetic Renal Diseases: The Emerging Role of Zebrafish Models. Cells. 2018, 7(9):130.
4. Naylor RW, et al. A novel nanoluciferase transgenic reporter measures proteinuria in zebrafish [published online ahead of print, 2022 Jun 15]. Kidney Int. 2022, S0085-2538(22)00452-5.

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