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Modeling Lysosomal Storage Diseases in the Zebrafish
1Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, United States.
Abstract:
Lysosomal storage diseases (LSDs) are a family of 70 metabolic disorders characterized by mutations in lysosomal proteins that lead to storage material accumulation, multiple-organ 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 organism-specific advantages and limitations, and discuss recent technological innovations that could provide potential solutions.
Insights
Zebrafish models offer valuable insights into lysosomal storage diseases (LSDs), a group of metabolic disorders. Studying these models aids in understanding disease mechanisms and developing new therapeutic strategies.
Area of Science:
- Biochemistry
- Genetics
- Developmental Biology
Background:
- Lysosomal storage diseases (LSDs) are a group of 70 inherited metabolic disorders.
- These conditions result from mutations in lysosomal proteins, leading to cellular accumulation of storage materials.
- LSDs often cause multi-organ pathologies, neurodegeneration, and premature death, highlighting the need for better therapies and understanding of disease origins.
Purpose of the Study:
- To review the utility of non-mammalian models for studying LSDs.
- To focus on zebrafish as a vertebrate model organism for LSD research.
- To explore how zebrafish models can advance the understanding of LSD etiology and identify novel therapeutic targets.
Main Methods:
- Review of published literature on zebrafish models of LSDs.
- Analysis of reported phenotypes in zebrafish LSD models.
- Discussion of the advantages and limitations of using zebrafish in LSD research.
- Exploration of technological innovations relevant to zebrafish-based LSD studies.
Main Results:
- Zebrafish exhibit significant genetic and metabolic similarities to mammals, making them suitable for modeling human diseases.
- The optical transparency and high-throughput capabilities of zebrafish offer unique advantages for studying LSDs.
- Various zebrafish LSD models have been developed, exhibiting relevant phenotypes.
Conclusions:
- Zebrafish represent a powerful and versatile model organism for investigating the complex mechanisms of LSDs.
- Further technological advancements can enhance the application of zebrafish models in discovering novel pathways and therapeutic strategies for LSDs.
- Non-mammalian models, particularly zebrafish, are crucial for advancing LSD research beyond traditional approaches.
