Modeling Lysosomal Storage Diseases in the Zebrafish

Abstract

Lysosomal storage diseases (LSDs) are a family of 70 metabolic disorders characterized by mutations in lysosomal proteins that lead to storage material accumulation, multipleorgan pathologies that often involve neurodegeneration, and early mortality in a significant number of patients. Along with the necessity for more effective therapies, there exists an unmet need for further understanding of disease etiology, which could uncover novel pathways and drug targets. Over the past few decades, the growth in knowledge of disease-associated pathways has been facilitated by studies in model organisms, as advancements in mutagenesis techniques markedly improved the efficiency of model generation in mammalian and non-mammalian systems. In this review we highlight non-mammalian models of LSDs, focusing specifically on the zebrafish, a vertebrate model organism that shares remarkable genetic and metabolic similarities with mammals while also conferring unique advantages such as optical transparency and amenability toward high-throughput applications. We examine published zebrafish LSD models and their reported phenotypes, address organismspecific advantages and limitations, and discuss recent technological innovations that could provide potential solutions.

Dysregulated adaptive immune response contributes to severe COVID-19

“…Consistent with our observation of elevated effector B cells in severely affected patients, high antibody titer was reported to be associated with disease severity and worse outcome both in COVID-19 and SARS, [8][9][10] suggesting that ADE accelerated severe disease. The Intravenous Immunoglobulin (IVIg), a polyclonal immunoglobulin G product, can bind the Fc receptors and thus block the ADE of viral infection.…”

A Great Catch for Investigating Inborn Errors of Metabolism—Insights Obtained from Zebrafish

“…Lysosomal storage disorders including types of neuronal ceroid lipofuscinoses (NCL), sphingolipidoses, and mucopolysaccharidosis (MPS) in the zebrafish model have just recently been extensively reviewed, therefore we will only highlight some of the most recent and striking advances [ 159 ].…”

Visualisation of cholesterol and ganglioside GM1 in zebrafish models of Niemann–Pick type C disease and Smith–Lemli–Opitz syndrome using light sheet microscopy

“…Increasingly, large mammals are used to model LSDs; these models offer advantages in translation of effects to humans, particularly due to their larger more complex brain (Gurda and Vite 2019 ). However, these experiments are both slow and costly (Zhang and Peterson 2020 ).…”

“…Zebrafish ( Danio rerio ) LSD models have risen dramatically over the past 20 years, now with more than 20 different LSDs, reviewed here (Zhang and Peterson 2020 ). Zebrafish are extremely useful for therapeutic advancement as they provide a model that is cheap, quick to breed and fast to develop.…”

“…A further growing advantage of zebrafish is their utility in high-throughput drug screening and toxicology assays, work that can significantly accelerate and reduce the costs of drug discovery (Wiley et al 2017 ). Finally, a major advantage over larger animals is their optical transparency in the larval stages, allowing easy visualisation of stains in vivo, without the need for sectioning (Zhang and Peterson 2020 ). One possible drawback of zebrafish is the lack of effective and accurate antibodies, especially for lysosomal proteins.…”