PUBLICATION
The abcc6a Gene Expression Is Required for Normal Zebrafish Development
- Authors
- Li, Q., Sadowski, S., Frank, M., Chai, C., Váradi, A., Ho, S.Y., Lou, H., Dean, M., Thisse, C., Thisse, B., and Uitto, J.
- ID
- ZDB-PUB-100719-4
- Date
- 2010
- Source
- The Journal of investigative dermatology 130(11): 2561-2568 (Journal)
- Registered Authors
- Chai, Chun-Li, Dean, Michael, Ho, Shiu-Ying, Lou, Hong, Thisse, Bernard, Thisse, Christine
- Keywords
- none
- MeSH Terms
-
- ATP-Binding Cassette Transporters/genetics*
- ATP-Binding Cassette Transporters/metabolism
- Amino Acid Sequence
- Animals
- Gene Expression Regulation, Developmental/physiology*
- Gene Knockdown Techniques
- Kidney Tubules, Proximal/embryology
- Kidney Tubules, Proximal/physiology
- Mice
- Models, Animal
- Molecular Sequence Data
- Oligonucleotides/genetics
- Oligonucleotides/pharmacology
- Phenotype
- Phylogeny
- Pseudoxanthoma Elasticum/genetics
- Zebrafish/embryology
- Zebrafish/genetics*
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 20596085 Full text @ J. Invest. Dermatol.
Citation
Li, Q., Sadowski, S., Frank, M., Chai, C., Váradi, A., Ho, S.Y., Lou, H., Dean, M., Thisse, C., Thisse, B., and Uitto, J. (2010) The abcc6a Gene Expression Is Required for Normal Zebrafish Development. The Journal of investigative dermatology. 130(11):2561-2568.
Abstract
Pseudoxanthoma elasticum (PXE) is caused by mutations in the ABCC6 gene, which encodes a putative efflux transporter, ABCC6. The zebrafish (Danio rerio) has two ABCC6-related sequences. To study the function of abcc6 during zebrafish development, the mRNA expression levels were measured using RT-PCR and in situ hybridization. The abcc6a showed a relatively high level of expression at 5 days post-fertilization (d.p.f.) and the expression was specific to the Kupffer's vesicles. The abcc6b expression was evident at 6 hours post-fertilization (h.p.f.) and remained high up to 8 d.p.f., corresponding to embryonic kidney proximal tubules. Morpholinos were designed to both genes to prevent pre-mRNA splicing and block translation. Injection of the abcc6a morpholinos into 1-4 cell zebrafish embryos decreased gene expression by 54-81%, and induced a phenotype, pericardial edema and curled tail associated with death at around 8 d.p.f. Microinjecting zebrafish embryos with full-length mouse Abcc6 mRNA together with the morpholino completely rescued this phenotype. No phenotypic changes were observed when the abcc6b gene morpholino was injected into embryos with knock-down efficiency of 100%. These results suggest that abcc6a is an essential gene for normal zebrafish development and provide insight into the function of ABCC6, the gene mutated in PXE.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping