PUBLICATION
Disrupted Copper Homeostasis and Impaired Retinal Development Caused by slc6a4a Deficiency in Zebrafish
- Authors
- Baloch, H.U., Jing, Y.Y., Shi, J.H., Wang, H.F., Wu, Y., Liu, J.X.
- ID
- ZDB-PUB-260715-17
- Date
- 2026
- Source
- Animals : an open access journal from MDPI 16: 2036 (Journal)
- Registered Authors
- Baloch, Hameed Ullah, Liu, Jing-xia
- Keywords
- Atp7b, copper homeostasis, retinal development, slc6a4a, tetrathiomolybdate
- MeSH Terms
- none
- PubMed
- 42450743 Full text @ Animals (Basel)
Citation
Baloch, H.U., Jing, Y.Y., Shi, J.H., Wang, H.F., Wu, Y., Liu, J.X. (2026) Disrupted Copper Homeostasis and Impaired Retinal Development Caused by slc6a4a Deficiency in Zebrafish. Animals : an open access journal from MDPI. 16:2036.
Abstract
Serotonin transporter Slc6a4a functions as a transporter in serotonin reuptake and is tightly linked with serotonergic regulation and stress responses. However, few studies have investigated its role in copper homeostasis and organogenesis in an in vivo vertebrate model. In this study, we demonstrate that slc6a4a deficiency (slc6a4a-/-) leads to copper accumulation, retinal developmental defects, and locomotor dysfunction in zebrafish specifically. Mechanistically, slc6a4a deficiency is associated with reduced atp7b and copper accumulation, which lead to reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress, and results in Caspase-3-mediated apoptosis and retinal degeneration. Specifically, tetrathiomolybdate (TTM), a pharmacological copper chelator, partially reduces ER stress and restores retinal defects. Additionally, ectopic expression of full-length atp7b mRNA partially restores retinal defects. These findings identify serotonin transporter Slc6a4a as a novel regulator in copper homeostasis and retinal development via the regulation of Atp7b in an in vivo vertebrate model. This study supports a mechanistic link between slc6a4a deficiency, copper overload, and retinal defects and highlights copper chelation as an alternative therapeutic strategy in individuals with Slc6a4 deficiency.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping