PUBLICATION
Functional characterization of the Bcl-2 gene family in the zebrafish
- Authors
- Kratz, E., Eimon, P.M., Mukhyala, K., Stern, H., Zha, J., Strasser, A., Hart, R., and Ashkenazi A.
- ID
- ZDB-PUB-060816-5
- Date
- 2006
- Source
- Cell death and differentiation 13(10): 1631-1640 (Journal)
- Registered Authors
- Kratz, Erica, Stern, Howard
- Keywords
- apoptosis, intrinsic pathway, Bcl-2 family
- MeSH Terms
-
- Animals
- Apoptosis/genetics
- Apoptosis/radiation effects
- Base Sequence
- Gamma Rays
- Gene Expression Regulation, Developmental
- Genes, bcl-2*
- Mammals/genetics
- Multigene Family
- Oligodeoxyribonucleotides, Antisense/genetics
- Phylogeny
- RNA Interference
- Zebrafish/embryology
- Zebrafish/genetics*
- PubMed
- 16888646 Full text @ Cell Death Differ.
Citation
Kratz, E., Eimon, P.M., Mukhyala, K., Stern, H., Zha, J., Strasser, A., Hart, R., and Ashkenazi A. (2006) Functional characterization of the Bcl-2 gene family in the zebrafish. Cell death and differentiation. 13(10):1631-1640.
Abstract
Members of the Bcl-2 protein family control the intrinsic apoptosis pathway. To evaluate the importance of this family in vertebrate development, we investigated it in the zebrafish (Danio rerio). We found that the zebrafish genome encodes structural and functional homologs of most mammalian Bcl-2 family members, including multi-Bcl-2-homology (BH) domain proteins and BH3-only proteins. Apoptosis induction by gamma-irradiation required zBax1 and zPuma, and could be prevented by overexpression of homologs of prosurvival Bcl-2 family members. Surprisingly, zebrafish Bax2 (zBax2) was homologous to mammalian Bax by sequence and synteny, yet demonstrated functional conservation with human Bak. Morpholino knockdown of both zMcl-1a and zMcl-1b revealed their critical role in early embryonic zebrafish development, and in the modulation of apoptosis activation through the extrinsic pathway. These data indicate substantial functional similarity between zebrafish and mammalian Bcl-2 family members, and establish the zebrafish as a relevant model for studying the intrinsic apoptosis pathway.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping