Zebrafish as a Model of Kidney Disease

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.