Zebrafish as a Model for Drug Screening in Genetic Kidney Diseases

Abstract

Genetic disorders account for a wide range of renal diseases emerging during childhood and adolescence. Due to the utilization of modern biochemical and biomedical techniques, the number of identified disease-associated genes is increasing rapidly. Modeling of congenital human disease in animals is key to our understanding of the biological mechanism underlying pathological processes and thus developing novel potential treatment options. The zebrafish (Danio rerio) has been established as a versatile small vertebrate organism that is widely used for studying human inherited diseases. Genetic accessibility in combination with elegant experimental methods in zebrafish permit modeling of human genetic diseases and dissecting the perturbation of underlying cellular networks and physiological processes. Beyond its utility for genetic analysis and pathophysiological and mechanistic studies, zebrafish embryos, and larvae are amenable for phenotypic screening approaches employing high-content and high-throughput experiments using automated microscopy. This includes large-scale chemical screening experiments using genetic models for searching for disease-modulating compounds. Phenotype-based approaches of drug discovery have been successfully performed in diverse zebrafish-based screening applications with various phenotypic readouts. As a result, these can lead to the identification of candidate substances that are further examined in preclinical and clinical trials. In this review, we discuss zebrafish models for inherited kidney disease as well as requirements and considerations for the technical realization of drug screening experiments in zebrafish.

Exploring Key Challenges of Understanding the Pathogenesis of Kidney Disease in Bardet–Biedl Syndrome

“…96 Several advances in kidney-related ciliopathies have been derived from zebrafish studies. 97 Nevertheless, major studies on zebrafish BBS models focused on developmental extrarenal defects, in particular the morphogenesis of the Kupffer vesicle, a ciliated organ essential for the establishment of left-right symmetry, 98 while relatively few studies investigated kidney phenotypes. The latter has been described in at least 4 BBS models.…”

Impact of post-hatching maturation on the pharmacokinetics of paracetamol in zebrafish larvae

“…Although experiments with larva have many advantages, studying an organism during its development will require understanding of the effect of maturation on the studied feature. Zebrafish development is rapid, showing embryogenesis within 3 dpf 21 , liver budding from 1 dpf and growth from 2 dpf 22 , development of a functional renal system after 2 dpf 23 , and presence of a gastro-intestinal (GI) tract from 1–4 dpf 24 , reaching adulthood in 3 months 25 . These developmental and maturation processes in the first days post fertilisation are expected to have an impact on the absorption and elimination of compounds.…”

Visual Contrast Modulates Operant Learning Responses in Larval Zebrafish

“…Larval zebrafish are amenable to high-throughput screen due to their transparency, small size and high permeability to small molecules (Kokel et al, 2010; Rihel et al, 2010). Though most systems are designed for drug or genetic screens (Rihel et al, 2010; Gehrig et al, 2018; Yang X. et al, 2018), here we have developed a high-throughput behavioral training system with custom supported software suites. Compared with previous work (Pelkowski et al, 2011; Hinz et al, 2013), the BLITZ software has enabled a fully automatic control of video capture, online image processing, visual pattern presentation and electroshocks delivery, making it an easily adaptable system for various purposes.…”