Zinc dysregulation in slc30a8 ( znt8 ) mutant zebrafish leads to blindness and disrupts bone mineralisation
Zinc dysregulation in slc30a8 ( znt8 ) mutant zebrafish leads to blindness and disrupts bone mineralisation
Abstract Zinc is an essential cofactor for many cellular processes including gene transcription, insulin secretion and retinal function. Excessive free Zn2+ is highly toxic and consequently intracellular zinc is tightly controlled by a system of transporters, metallothioneins (MTs) and storage vesicles. Here we describe the developmental consequences of a missense allele of zinc efflux transporter slc30a8 (znt8) in zebrafish. Homozygous slc30a8hu1798 larvae are virtually blind and develop very little or no bone mineral. We show that zinc is stored in pigmented cells (melanophores) of healthy larvae but in slc30a8hu1798 mutants it instead accumulates in the bone and brain. Supporting a role for pigment cells in zinc homeostasis, nacre zebrafish, which lack melanophores, also show disrupted zinc homeostasis. The photoreceptors of slc30a8hu1798 fish are severely depleted while those of nacre fish are enriched with zinc. We propose that developing zebrafish utilise pigmented cells as a zinc storage organ, and that Slc30a8 is required for transport of zinc into these cells and into photoreceptors.
Molero Sof¨aa Iba?ez、Zang Jingjing、Wilson Stephen W.、Peterson-Maduro Josi、Mackay Eirinn W、Schulte-Merker Stefan、Neuhauss Stephan C.F.、Tirathdas Lavitasha Harjani
Department of Cell and Developmental Biology, University College LondonInstitute of Molecular Life Sciences, University of ZurichDepartment of Cell and Developmental Biology, University College LondonHubrecht Institute?aKNAW & University Medical Centre UtrechtDepartment of Cell and Developmental Biology, University College London||Hubrecht Institute?aKNAW & University Medical Centre UtrechtHubrecht Institute?aKNAW & University Medical Centre Utrecht||Institute of Cardiovascular Organogenesis and Regeneration, Faculty of Medicine, University of M¨1nsterInstitute of Molecular Life Sciences, University of ZurichDepartment of Cell and Developmental Biology, University College London
遗传学生物化学分子生物学
Molero Sof¨aa Iba?ez,Zang Jingjing,Wilson Stephen W.,Peterson-Maduro Josi,Mackay Eirinn W,Schulte-Merker Stefan,Neuhauss Stephan C.F.,Tirathdas Lavitasha Harjani.Zinc dysregulation in slc30a8 ( znt8 ) mutant zebrafish leads to blindness and disrupts bone mineralisation[EB/OL].(2025-03-28)[2025-05-10].https://www.biorxiv.org/content/10.1101/2020.09.02.279182.点此复制
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