PUBLICATION
Transferrin-a modulates hepcidin expression in zebrafish embryos
- Authors
- Fraenkel, P.G., Gibert, Y., Holzheimer, J.L., Lattanzi, V.J., Burnett, S.F., Dooley, K.A., Wingert, R.A., and Zon, L.I.
- ID
- ZDB-PUB-081203-35
- Date
- 2009
- Source
- Blood 113(12): 2843-2850 (Journal)
- Registered Authors
- Dooley, Kim, Fraenkel, Paula, Gibert, Yann, Wingert, Rebecca, Zon, Leonard I.
- Keywords
- none
- MeSH Terms
-
- Mutation
- Hepcidins
- Anemia, Hypochromic/chemically induced
- Anemia, Hypochromic/embryology
- Anemia, Hypochromic/genetics
- Iron/metabolism*
- Iron/pharmacology
- Species Specificity
- Gene Expression Regulation, Developmental/drug effects
- Gene Expression Regulation, Developmental/physiology*
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Gene Knockdown Techniques
- Humans
- Receptors, Transferrin/antagonists & inhibitors
- Receptors, Transferrin/genetics
- Receptors, Transferrin/physiology
- Erythropoiesis/drug effects
- Erythropoiesis/genetics
- Molecular Sequence Data
- Sequence Alignment
- Sequence Homology, Amino Acid
- Antimicrobial Cationic Peptides/biosynthesis*
- Antimicrobial Cationic Peptides/genetics
- Cation Transport Proteins/genetics
- Amino Acid Sequence
- Zebrafish Proteins/biosynthesis
- Zebrafish Proteins/deficiency
- Zebrafish Proteins/genetics
- Zebrafish Proteins/physiology*
- Phenylhydrazines/toxicity
- Organ Specificity
- Zebrafish/embryology
- Animals
- Transferrin/deficiency
- Transferrin/genetics
- Transferrin/physiology*
- PubMed
- 19047682 Full text @ Blood
Citation
Fraenkel, P.G., Gibert, Y., Holzheimer, J.L., Lattanzi, V.J., Burnett, S.F., Dooley, K.A., Wingert, R.A., and Zon, L.I. (2009) Transferrin-a modulates hepcidin expression in zebrafish embryos. Blood. 113(12):2843-2850.
Abstract
The iron regulatory hormone hepcidin is transcriptionally upregulated in response to iron loading, but the mechanisms by which iron levels are sensed are not well understood. Large-scale genetic screens in the zebrafish have resulted in the identification of hypochromic anemia mutants with a range of mutations affecting conserved pathways in iron metabolism and heme synthesis. We hypothesized that transferrin plays a critical role both in iron transport and in regulating hepcidin expression in zebrafish embryos. Here we report the identification and characterization of the zebrafish hypochromic anemia mutant, gavi, which exhibits transferrin-deficiency due to mutations in transferrin-a. Morpholino knockdown of transferrin-a in wild type embryos reproduced the anemia phenotype and decreased somite and terminal gut iron staining, while co-injection of transferrin-a cRNA partially restored these defects. Embryos with transferrin-a or transferrin receptor 2 (TfR2) deficiency exhibited low levels of hepcidin expression, however anemia, in the absence of a defect in the transferrin pathway, failed to impair hepcidin expression. These data indicate that transferrin-a transports iron and that hepcidin expression is regulated by a transferrin-a-dependent pathway in the zebrafish embryo.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping