MINI REVIEW article
Front. Cell Dev. Biol.
Sec. Membrane Traffic and Organelle Dynamics
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1637005
This article is part of the Research Topic2024 International Lowe Syndrome Symposium: Advances and ProceedingsView all articles
Modelling Lowe syndrome and Dent-2 disease using zebrafish
Provisionally accepted
- The University of Manchester, Manchester, United Kingdom
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Lowe syndrome and Dent-2 disease are caused by mutations in the gene encoding OCRL, an inositol 5-phosphatase. The phenotype manifests in the eyes, brain and kidney, with the extra-renal features milder in the case of Dent-2 disease. Zebrafish has been used to study OCRL function in vivo and to successfully model these two rare genetic conditions. OCRL-deficient zebrafish have neurodevelopmental defects, which may lie downstream of disrupted endosomal trafficking or primary cilia function. OCRL-deficient zebrafish also have a renal tubular phenotype, with defective endocytosis, abnormal lysosomal function, and shortening of the renal tubule. These defects can account for the low molecular weight proteinuria seen in Lowe syndrome and Dent-2 disease and may explain the other renal features seen in both conditions. Chemical and genetic rescue experiments indicate that zebrafish can be used to test potential therapeutic approaches for Lowe syndrome and Dent-2 disease, raising the possibility of a phenotypic screen for these conditions in zebrafish. Alongside other models, zebrafish has proven its worth in studying Lowe syndrome and Dent-2 disease and should continue to serve as a valuable model going forwards.
Keywords: Zebrafish, Lowe syndrome, Dent-2 disease, Neurological, Renal, Endocytosis, Ciliogenesesis
Received: 28 May 2025; Accepted: 16 Jul 2025.
Copyright: © 2025 Lowe. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Martin Lowe, The University of Manchester, Manchester, United Kingdom
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