The abcc6a Gene Expression Is Required for Normal Zebrafish Development
- Li, Q., Sadowski, S., Frank, M., Chai, C., Váradi, A., Ho, S.Y., Lou, H., Dean, M., Thisse, C., Thisse, B., and Uitto, J.
- 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
- MeSH Terms
- ATP-Binding Cassette Transporters/genetics*
- ATP-Binding Cassette Transporters/metabolism
- Amino Acid Sequence
- Gene Expression Regulation, Developmental/physiology*
- Gene Knockdown Techniques
- Kidney Tubules, Proximal/embryology
- Kidney Tubules, Proximal/physiology
- Models, Animal
- Molecular Sequence Data
- Pseudoxanthoma Elasticum/genetics
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- 20596085 Full text @ J. Invest. Dermatol.
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.
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
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes