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.

中文翻译：

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在斑马鱼中模拟溶酶体贮积病。

溶酶体贮积病（LSD）是70个代谢紊乱的家族，其特征是溶酶体蛋白质突变导致贮藏材料积聚，多器官病变（通常涉及神经退行性变）以及大量患者的早期死亡。随着更有效疗法的必要性，对疾病病因学的进一步理解存在未满足的需求，这可能会发现新的途径和药物靶标。在过去的几十年中，模型生物的研究促进了疾病相关途径的知识的增长，因为诱变技术的进步显着提高了哺乳动物和非哺乳动物系统中模型生成的效率。在这篇评论中，我们重点介绍了LSD的非哺乳动物模型，重点是斑马鱼，一种脊椎动物模型生物，与哺乳动物具有显着的遗传和代谢相似性，同时还具有独特的优势，例如光学透明性和高通量应用的适应性。我们研究了已发表的斑马鱼LSD模型及其报告的表型，探讨了特定于有机体的优势和局限性，并讨论了可以提供潜在解决方案的最新技术创新。