Department of Molecular Medicine and Pathology, The University of Auckland, Auckland 1142, New Zealand.
Department of Physiology, BioSciences Institute, University College Cork, T12 XF62 Cork, Ireland.
Cells. 2021 Dec 21;11(1):6. doi: 10.3390/cells11010006.
The development over the past 50 years of a variety of cell lines and animal models has provided valuable tools to understand the pathophysiology of nephropathic cystinosis. Primary cultures from patient biopsies have been instrumental in determining the primary cause of cystine accumulation in the lysosomes. Immortalised cell lines have been established using different gene constructs and have revealed a wealth of knowledge concerning the molecular mechanisms that underlie cystinosis. More recently, the generation of induced pluripotent stem cells, kidney organoids and tubuloids have helped bridge the gap between in vitro and in vivo model systems. The development of genetically modified mice and rats have made it possible to explore the cystinotic phenotype in an in vivo setting. All of these models have helped shape our understanding of cystinosis and have led to the conclusion that cystine accumulation is not the only pathology that needs targeting in this multisystemic disease. This review provides an overview of the in vitro and in vivo models available to study cystinosis, how well they recapitulate the disease phenotype, and their limitations.
在过去的 50 年中，各种细胞系和动物模型的发展为理解胱氨酸贮积症的病理生理学提供了有价值的工具。从患者活检中获得的原代培养物对于确定溶酶体中胱氨酸积累的主要原因非常重要。使用不同的基因构建体建立了永生化细胞系，并揭示了许多关于胱氨酸贮积症基础的分子机制的知识。最近，诱导多能干细胞、肾脏类器官和肾小管样细胞的产生有助于弥合体外和体内模型系统之间的差距。基因修饰小鼠和大鼠的发展使得在体内环境中探索胱氨酸贮积症表型成为可能。所有这些模型都有助于我们加深对胱氨酸贮积症的理解，并得出结论，胱氨酸积累并不是这种多系统疾病中唯一需要靶向的病理学。这篇综述概述了可用于研究胱氨酸贮积症的体外和体内模型，以及它们对疾病表型的再现程度和局限性。
