ArticlePLoS genetics2017
Zebrafish slc30a10 deficiency revealed a novel compensatory mechanism of Atp2c1 in maintaining manganese homeostasis.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Biomarkers of environmental manganese exposure and associations with childhood neurodevelopment: a systematic review and meta-analysis.Environmental health : a global access science source · 2020Pooled it
- Manganese: biology, physiology and role in disease.Cell discovery · 2026Review
- Overlaps in mammalian iron and manganese homeostasis: recent advances.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Manganese Exposure: Delayed Effects and Biomarkers in adult male and female Wistar rats.Molecular neurobiology · 2026Article
- Zinc Transporter Gene Variants (SLC30A and SLC39A) in Human Disease: From Metal Homeostasis Disruption to Convergent Signaling Pathways.Human mutation · 2026Review
- MnOAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Role of manganese in brain health and disease: Focus on oxidative stress.Free radical biology & medicine · 2025Review
- Bone cell differentiation and mineralization in wild-type and osteogenesis imperfecta zebrafish are compromised by per- and poly-fluoroalkyl substances (PFAS).Scientific reports · 2025Article
- The Intestinal Transporter SLC30A1 Plays a Critical Role in Regulating Systemic Zinc Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- A Novel Role for the Longevity-Associated Protein SLC39A11 as a Manganese Transporter.Research (Washington, D.C.) · 2024Article
- Trace metal elements: a bridge between host and intestinal microorganisms.Science China. Life sciences · 2023Review
- Flight for fish in drug discovery: a review of zebrafish-based screening of molecules.Biology letters · 2023Review
- The Zinc Transporter SLC39A10 Plays an Essential Role in Embryonic Hematopoiesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- MnOChemical science · 2022Article
- Metal transporter Slc30a1 controls pharyngeal neural crest differentiation via the zinc-Snai2-Jag1 cascade.MedComm · 2021Article
- Genome-wide CRISPR-Cas9 screens identify mechanisms of BET bromodomain inhibitor sensitivity.iScience · 2021Article
- Characterization of in vitro models of SLC30A10 deficiency.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2021Article
- Iron-responsive-like elements and neurodegenerative ferroptosis.Learning & memory (Cold Spring Harbor, N.Y.) · 2020Review
- Maintaining Translational Relevance in Animal Models of Manganese Neurotoxicity.The Journal of nutrition · 2020Article
- Brain manganese and the balance between essential roles and neurotoxicity.The Journal of biological chemistry · 2020Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent studies found that mutations in the human SLC30A10 gene, which encodes a manganese (Mn) efflux transporter, are associated with hypermanganesemia with dystonia, polycythemia, and cirrhosis (HMDPC). However, the relationship between Mn metabolism and HMDPC is poorly understood, and no specific treatments are available for this disorder. Here, we generated two zebrafish slc30a10 mutant lines using the CRISPR/Cas9 system. Compared to wild-type animals, mutant adult animals developed significantly higher systemic Mn levels, and Mn accumulated in the brain and liver of mutant embryos in response to exogenous Mn. Interestingly, slc30a10 mutants developed neurological deficits in adulthood, as well as environmental Mn-induced manganism in the embryonic stage; moreover, mutant animals had impaired dopaminergic and GABAergic signaling. Finally, mutant animals developed steatosis, liver fibrosis, and polycythemia accompanied by increased epo expression. This phenotype was rescued partially by EDTA- CaNa2 chelation therapy and iron supplementation. Interestingly, prior to the onset of slc30a10 expression, expressing ATP2C1 (ATPase secretory pathway Ca2+ transporting 1) protected mutant embryos from Mn exposure, suggesting a compensatory role for Atp2c1 in the absence of Slc30a10. Notably, expressing either wild-type or mutant forms of SLC30A10 was sufficient to inhibit the effect of ATP2C1 in response to Mn challenge in both zebrafish embryos and HeLa cells. These findings suggest that either activating ATP2C1 or restoring the Mn-induced trafficking of ATP2C1 can reduce Mn accumulation, providing a possible target for treating HMDPC.
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