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July 22, 2019

Zebrafish: How Can They Help Us?

I have enjoyed working with laboratory zebrafish since 2003.  Zebrafish have become a very well accepted model organism for human disease due to rapid breeding, fast development, transparent embryos, and conservation of 70% of human genes.  Several human diseases have been successfully modeled using zebrafish such as acute lymphoblastic leukemia, melanoma, and Duchenne muscular dystrophy. The majority of my time with zebrafish was spent in the Vanderbilt University system where I was involved in diverse research areas such as gastrulation, fetal alcohol syndrome, holoprosencephaly, Menkes Disease, and obesity. I discovered that I like contributing to the discovery or development of something that can potentially make a difference in people’s lives.

Zebrafish are a particularly great model for studying kidney disease because their kidneys are both structurally and functionally similar to human kidneys. The adult zebrafish kidney, known as mesonephros, is a single flat structure attached to the dorsal body wall and composed of approximately 450 functional units known as nephrons.  The zebrafish nephrons are highly bifurcated consisting of proximal convoluted tubules, proximal straight tubules, and distal early and late segments, which connect to the collecting ducts that are fused to the cloaca.  Unlike humans, zebrafish have the ability to regenerate new nephrons in response to injury as well as continually add new nephrons as they age. 

One way to induce damage to the zebrafish kidney is by injecting the antibiotic gentamicin into the intraperitoneal cavity of the adult fish.  Gentamicin causes injury in the proximal tubule of the nephron by inducing epithelial cell death. This process includes the shedding of the basement membrane of the proximal tubule, loss of the brush border, and loss of functionality.  Damage can be assessed by locating cellular casts shed from tubules in the water at 1 day post injection.  Histological methods such as H&E staining, fluorescent dextran, and alkaline phosphatase reactivity with Elf-97 at various time points post-injection can also determine the extent of damage and onset of regeneration.

Due to their optical clarity, developmental stage zebrafish provide a distinctive opportunity to visualize cell dynamics in real-time and document cell activity in vivo. Understanding kidney injury and regeneration in zebrafish could provide invaluable information in preventing and treating acute kidney injury as well as other kidney diseases in humans, as many molecular mechanisms are conserved between these groups. 

I have had the pleasure of working for Arkana’s zebrafish research program for almost three years as an aquatic research assistant.  One of the main projects I am currently involved in is creating different kidney disease models in zebrafish. Our group is particularly interested in developing new treatments that can halt the progression of kidney injury and developing tools that will enable early detection of these diseases. Working at Arkana has created a deeper connection to my work because it is so much closer to actual people who need new or better treatment options for disease.

Find more information about our zebrafish lab and services here