Zebrafish as a Model of Kidney Disease

Abstract

Animal models have been an invaluable means to advance biomedical research as they provide experimental avenues for cellular and molecular investigations of disease pathology. The zebrafish (Danio rerio) is a good alternative to mammalian models that can be used to apply powerful genetic experimental methods normally used in invertebrates to answer questions about vertebrate development and disease. In the case of the kidney, the zebrafish has proven itself to be an applicable and versatile experimental system, mainly due to the simplicity of its pronephros, which contains two nephrons that possess conserved structural and physiological aspects with mammalian nephrons. Numerous genes that were not previously related to kidney conditions have now been linked to renal diseases by applying genetic screening with the zebrafish. In fact, a large collection of mutations that affect nephron formation and function were generated through phenotype-based forward screens. Complementary reverse genetic approaches have also been insightful, with methods spanning the use of antisense morpholino oligonucleotides to genome editing approaches such as the CRISPR/Cas9 system, to selectively knock down or knock out genes of interest to see if they produce kidney phenotypes. Acute kidney injury (AKI) has also been easily modeled in the zebrafish by injecting nephrotoxins, directly inducing damage through surgical intervention, or by generating transgenic lines that express compounds in a tissue-specific manner that when exposed to certain drugs promote an apoptotic response within cells. In this chapter, we provide an overview of these various approaches as well as discuss many of the contributions that have been achieved through the use of zebrafish to model kidney disease.

Dissecting hematopoietic and renal cell heterogeneity in adult zebrafish at single-cell resolution using RNA sequencing

“…These functions are performed by highly conserved structures, including the glomerulus, segmented nephron tubules, and collecting duct ( Vize et al, 1997 ). The simplicity of the kidney structure in the zebrafish embryo has propelled the model forward as one of the best for studying kidney development and function ( Drummond et al, 1998 ; Morales and Wingert, 2017 ). Studies of the adult zebrafish kidney have also uncovered remarkable regenerative capacity and the identification of stem cell populations that generate new nephrons in response to injury ( Diep et al, 2011 ).…”

The zebrafish kidney mutant zeppelin reveals that brca2/fancd1 is essential for pronephros development

“…Among nephron cell types, identification of the pathways that impact podocyte specification and differentiation has exceptionally high clinical importance because podocyte defects initiate a vast majority of chronic kidney disease states (Nagata, 2016). The central importance of podocytes, as well as their conservation across vertebrates, has led to their increasing study in a number of animal models, including the zebrafish (Morales and Wingert, 2017). …”

An intestinal cell type in zebrafish is the nexus for the SARS-CoV-2 receptor and the Renin-Angiotensin-Aldosterone System that contributes to COVID-19 comorbidities

“…The molecular genetic bases of complex diseases like COVID-19 are often illuminated by investigations in model organisms (Wangler et al, 2017). Among vertebrate models for human disease, zebrafish (Danio rerio) is a workhorse for understanding COVID-19-related organs, including heart and vasculature, kidney, liver, and many others (e.g., (Bournele and Beis, 2016;Goessling and Sadler, 2015;Morales and Wingert, 2017)). Zebrafish can even contribute to understanding communicable human diseases (Bouz and Al Hasawi, 2018;Sullivan et al, 2017); for example, transgenic cell markers and body transparency helped identify a specific macrophage type as the long-sought reservoir for asymptomatic tuberculosis (Clay et al, 2007).…”