Zhang T, Peterson R T
Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, United States.
Front Mol Biosci. 2020 May 6;7:82. doi: 10.3389/fmolb.2020.00082. eCollection 2020.
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.
溶酶体贮积症（LSDs）是一类包含70种代谢紊乱的疾病，其特征为溶酶体蛋白发生突变，导致储存物质积累、多器官病变（常涉及神经退行性变），且大量患者过早死亡。除了需要更有效的治疗方法外，对于进一步了解疾病病因也存在未满足的需求，这可能会揭示新的途径和药物靶点。在过去几十年中，模式生物研究推动了与疾病相关途径知识的增长，因为诱变技术的进步显著提高了哺乳动物和非哺乳动物系统中模型构建的效率。在本综述中，我们重点介绍LSDs的非哺乳动物模型，特别关注斑马鱼，这是一种脊椎动物模式生物，与哺乳动物具有显著的遗传和代谢相似性，同时还具有如光学透明性和适合高通量应用等独特优势。我们研究已发表的斑马鱼LSD模型及其报道的表型，探讨该生物体特有的优势和局限性，并讨论近期可能提供潜在解决方案的技术创新。
