Abstract

Iron, copper, zinc, and eight other minerals are classified as essential trace elements because they present in minute in vivo quantities and are essential for life. Because either excess or insufficient levels of trace elements can be detrimental to life (causing human diseases such as iron-deficiency anemia, hemochromatosis, Menkes syndrome and Wilson's disease), the endogenous levels of trace minerals must be tightly regulated. Many studies have demonstrated the existence of systems that maintain trace element homeostasis, and these systems are highly conserved in multiple species ranging from yeast to mice. As a model for studying trace mineral metabolism, the zebrafish is indispensable to researchers. Several large-scale mutagenesis screens have been performed in zebrafish, and these screens led to the identification of a series of metal transporters and the generation of several mutagenesis lines, providing an in-depth functional analysis at the system level. Moreover, because of their developmental advantages, zebrafish have also been used in mineral metabolism-related chemical screens and toxicology studies. Here, we systematically review the major findings of trace element homeostasis studies using the zebrafish model, with a focus on iron, zinc, copper, selenium, manganese, and iodine. We also provide a homology analysis of trace mineral transporters in fish, mice and humans. Finally, we discuss the evidence that zebrafish is an ideal experimental tool for uncovering novel mechanisms of trace mineral metabolism and for improving approaches to treat mineral imbalance-related diseases.

Highlights

  • As children of the Earth, humans are intimately connected to our surroundings in many ways, and the relationship between humans and minerals is perhaps the most enigmatic

  • The results suggest that both tf-a and tfR2 are required for hepcidin expression, whereas tfR1a and dmt1 are required for increasing hepcidin expression in response to iron loading (Fraenkel et al, 2009)

  • The generation of various zebrafish knockdown and knockout models has greatly facilitated the identification of novel genes and mechanisms that underlie mineral metabolism, with respect to iron and copper, which produce characteristic phenotypic changes when their concentrations are altered

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Summary

INTRODUCTION

As children of the Earth, humans are intimately connected to our surroundings in many ways, and the relationship between humans and minerals is perhaps the most enigmatic. Our current knowledge regarding these regulatory factors has come primarily from studies using model organisms ranging from yeast to mice Among these species, the zebrafish (Danio rerio) has been a valuable vertebrate system with several unique advantages. Aside from transport and storage proteins, Hepcidin—a peptide hormone released by the liver—plays an important role in regulating iron levels by binding to Fpn and promoting its internalization. Other factors such as oxidoreductases [e.g., Duodenal Cytochrome b (Dytb), Ceruloplasmin (Cp), Hephaestin (Heph), and STEAP3) and modulatory proteins (e.g., Hemochromatosis (HFE), Hemojuvelin (HJV), Iron Regulatory Protein (IRP) 1/2, and Transmembrane Serine Protease 6 (TMPRSS6)] play an active role in iron metabolism (Muckenthaler and Lill, 2012; Srai and Sharp, 2012). Interacts with mRNA to control the levels of iron inside cells/N.D

H Ubiquitous M Ubiquitous Z Blood
H Pancreatic islet M Ubiquitous Z Ubiquitous
H Ubiquitous M Ubiquitous Z Liver
Findings
CONCLUSIONS

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