PUBLICATION
Suppression of apoptosis by bcl-2-overexpression in lymphoid cells of transgenic zebrafish
- Authors
- Langenau, D.M., Jette, C., Berghmans, S., Palomero, T., Kanki, J.P., Kutok, J.L., and Look, A.T.
- ID
- ZDB-PUB-041228-25
- Date
- 2005
- Source
- Blood 105(8): 3278-3285 (Journal)
- Registered Authors
- Jette, Cicely A., Kanki, John, Langenau, David, Look, A. Thomas, Palomero, Teresa
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Animals, Genetically Modified
- Apoptosis/drug effects
- Apoptosis/physiology*
- Apoptosis/radiation effects
- B-Lymphocytes/cytology
- B-Lymphocytes/physiology*
- Conserved Sequence
- Dexamethasone/pharmacology
- Gene Expression/physiology
- Gene Expression/radiation effects
- Glucocorticoids/pharmacology
- Green Fluorescent Proteins/genetics
- Leukemia, T-Cell/physiopathology
- Proto-Oncogene Proteins c-bcl-2/genetics*
- Proto-Oncogene Proteins c-bcl-2/metabolism
- Proto-Oncogene Proteins c-myc/physiology
- Recombinant Fusion Proteins/genetics
- Recombinant Fusion Proteins/metabolism
- T-Lymphocytes/cytology
- T-Lymphocytes/physiology*
- Thymus Gland/cytology
- Zebrafish
- PubMed
- 15618471 Full text @ Blood
Citation
Langenau, D.M., Jette, C., Berghmans, S., Palomero, T., Kanki, J.P., Kutok, J.L., and Look, A.T. (2005) Suppression of apoptosis by bcl-2-overexpression in lymphoid cells of transgenic zebrafish. Blood. 105(8):3278-3285.
Abstract
The zebrafish is an attractive vertebrate model for genetic studies of development, apoptosis, and cancer. Here we describe a transgenic zebrafish line in which T- and B-lymphoid cells express a fusion transgene that encodes the zebrafish bcl-2 protein fused to the enhanced green fluorescence protein (EGFP). Targeting EGFP-bcl-2 to the developing thymocytes of transgenic fish resulted in a 2.5-fold increase in thymocyte numbers and a 1.8-fold increase in GFP-labeled B cells in the kidney marrow. Fluorescent microscopic analysis of living rag2-EGFP-bcl-2 transgenic fish showed that their thymocytes were resistant to irradiation- and dexamethasone-induced apoptosis, when compared to control rag2-GFP transgenic zebrafish. To test the ability of bcl-2 to block irradiation-induced apoptosis in malignant cells, we compared the responsiveness of Myc-induced leukemias with and without EGFP-bcl-2 expression in living transgenic zebrafish. T-cell leukemias induced by the rag2-EGFP-Myc transgene were ablated by irradiation, whereas leukemias in double transgenic fish expressing both Myc and EGFP-bcl-2 were resistant to irradiation-induced apoptotic cell death. The forward genetic capacity of the zebrafish model system and the ability to monitor GFP-positive thymocytes in vivo make this an ideal transgenic line for modifier screens designed to identify genetic mutations or small molecules that modify bcl-2-mediated anti-apoptotic pathways.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping