The zebrafish mutant gene chardonnay (cdy) encodes divalent metal transporter 1 (DMT1).
Abstract
Iron is an essential nutrient required for the function of all cells, most notably for the production of hemoglobin in red blood cells. Defects in the mechanisms of iron absorption, storage, or utilization can lead to disorders of iron-limited erythropoiesis or iron overload. In an effort to further understand these processes, we have used the zebrafish as a genetic system to study vertebrate iron metabolism. Here we characterized the phenotype of chardonnay (cdy), a zebrafish mutant with hypochromic, microcytic anemia, and positioned the mutant gene on linkage group 11. The cdy gene was isolated by a functional genomics approach in which we used a combination of expression studies, sequence analyses, and radiation hybrid panel mapping. We identified erythroid-specific genes using a whole embryo mRNA in situ hybridization screen and placed these genes on the zebrafish genomic map. One of these genes encoded the iron transporter divalent metal transporter 1 (DMT1) and colocalized with the cdy gene. We identified a nonsense mutation in the cdy allele and demonstrated that, whereas wild-type zebrafish DMT1 protein can transport iron, the truncated protein expressed in cdy mutants is not functional. Our studies further demonstrate the conservation of iron metabolism in vertebrates and suggest the existence of an alternative pathway of intestinal and red blood cell iron uptake.
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Homologous proteins in yeast, flies, and zebrafish also transport iron and similar divalent cations.
“Homologous proteins in yeast, 63 flies, 64 and zebrafish 65 also transport iron and similar divalent cations.”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [65]
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- Authors
- Donovan, A.
- Affiliations
- Boston Children's Hospital (US)
- Corresponding author
- Donovan, A.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2002-08-22
- Volume
- 100
- Issue
- 13
- Pages
- 4655-4659
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2015831749
- Cited by
- 106
- References
- 46
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 1 · 2014: 6 · 2013: 4 · 2012: 4
- FWCI
- 3.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK053298)
- National Center for Research Resources (R01RR015402)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- DMT1, iron metabolism, iron deficiency anemia, microcytic hypochromic anemia, erythropoiesis, zebrafish, nonsense mutation, radiation hybrid mapping, iron transport
- MeSH terms
- Solute Carrier Family 11, Member 2, Alleles, Amino Acid Sequence, Anemia, Hypochromic, Animals, Cell Line, Chromosome Mapping, Cloning, Molecular, Erythrocytes, Fetal Diseases, Fish Diseases, Genes, Humans, Intestinal Mucosa, Iron, Kidney, Genetic Linkage, Molecular Sequence Data, Organ Specificity, Phenotype, Recombinant Fusion Proteins, RNA, Messenger, Transfection, Zebrafish, Sequence Alignment, Sequence Homology, Amino Acid, In Situ Hybridization, Codon, Nonsense, Gene Expression Regulation, Developmental, Cation Transport Proteins, Iron-Binding Proteins
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