PUBLICATION
The zebrafish Znt1asa17 mutant reveals roles of zinc transporter-1a in embryonic development
- Authors
- Muraina, I.A., Bury, N.R., Scott, A., Graham, A., Hogstrand, C.
- ID
- ZDB-PUB-200403-148
- Date
- 2020
- Source
- Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) 60: 126496 (Journal)
- Registered Authors
- Bury, Nicolas
- Keywords
- Development, ERK1/2, Slc30a1, Zebrafish, Zinc
- MeSH Terms
-
- Amino Acids/genetics
- Amino Acids/metabolism
- Animals
- Carrier Proteins/genetics*
- Carrier Proteins/metabolism
- Embryonic Development/genetics*
- Homeostasis/genetics
- Mutation
- Zebrafish
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- Zinc/metabolism
- PubMed
- 32199393 Full text @ J. Trace Elem. Med. Biol.
Citation
Muraina, I.A., Bury, N.R., Scott, A., Graham, A., Hogstrand, C. (2020) The zebrafish Znt1asa17 mutant reveals roles of zinc transporter-1a in embryonic development. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 60:126496.
Abstract
Background Zinc is one of the vital micronutrients required through various developmental stages in animals. Zinc transporter-1 (ZnT1; Slc30a1) is essential in vertebrates for nutritional zinc uptake and cellular zinc extrusion. Knockout of ZnT1 is lethal in vertebrates and there are therefore few functional studies of this protein in vivo.
Methods In the present study we characterised the embryonic development in a zebrafish Znt1a mutant (Znt1asa17) which is lacking the last 40 amino acids of Znt1a as generated by TILLING. In parallel experiments, we compared the development of a zebrafish embryo Znt1a morphant (Znt1aMO) which was generated by knockdown of Znt1a using morpholino-modified oligonucliotides.
Results The homozygous Znt1asa17 embryo is viable, but displays a subtle phenotype informing on the biological roles of Znt1a. The Znt1asa17 fish have delayed development, including attenuated epiboly. They further show a decrease in phosphorylated extracellular signal-regulated kinases 1 and 2 (pERK1/2), retarded yolk resorption, and impaired clearance of free Zn2+ from the vitelline fluid and its storage in hatching gland cells. All these aberrations are milder versions of those observed upon knockdown of Znt1a by morpholinos. Interestingly, the phenotype could be rescued by addition of the cell-permeable zinc chelator, N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN) to the incubation medium and was aggravated by addition of zinc(II). Thus, the Znt1asa17 mutant has a reduced ability to handle zinc and can be characterised as a hypomorph.
Conclusion This study is the first to show that the last 40 amino acids of Znt1a are of importance for its role in zinc homeostasis and ability to activate the MAPK/ERK pathway contrary to what was previously thought.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping