ZFIN ID: ZDB-PUB-041228-25
Suppression of apoptosis by bcl-2-overexpression in lymphoid cells of transgenic zebrafish
Langenau, D.M., Jette, C., Berghmans, S., Palomero, T., Kanki, J.P., Kutok, J.L., and Look, A.T.
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
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.
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