Myc-induced T cell leukemia in transgenic zebrafish

Science. 2003 Feb 7;299(5608):887-90. doi: 10.1126/science.1080280.

Abstract

The zebrafish is an attractive model organism for studying cancer development because of its genetic accessibility. Here we describe the induction of clonally derived T cell acute lymphoblastic leukemia in transgenic zebrafish expressing mouse c-myc under control of the zebrafish Rag2 promoter. Visualization of leukemic cells expressing a chimeric transgene encoding Myc fused to green fluorescent protein (GFP) revealed that leukemias arose in the thymus, spread locally into gill arches and retro-orbital soft tissue, and then disseminated into skeletal muscle and abdominal organs. Leukemic cells homed back to the thymus in irradiated fish transplanted with GFP-labeled leukemic lymphoblasts. This transgenic model provides a platform for drug screens and for genetic screens aimed at identifying mutations that suppress or enhance c-myc- induced carcinogenesis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Lineage
  • Cell Transformation, Neoplastic*
  • Clone Cells
  • DNA-Binding Proteins / genetics
  • Disease Models, Animal*
  • Female
  • Fertilization in Vitro
  • Gene Expression Profiling
  • Genes, myc*
  • Green Fluorescent Proteins
  • Kidney / pathology
  • Leukemia-Lymphoma, Adult T-Cell* / genetics
  • Leukemia-Lymphoma, Adult T-Cell* / pathology
  • Leukemic Infiltration
  • Luminescent Proteins / metabolism
  • Male
  • Mice
  • Mutation
  • Neoplasm Transplantation
  • Olfactory Bulb / pathology
  • Promoter Regions, Genetic
  • Recombinant Fusion Proteins / metabolism
  • Spleen / pathology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology*
  • T-Lymphocytes / physiology
  • Thymus Gland / pathology
  • Transgenes
  • Zebrafish* / embryology
  • Zebrafish* / genetics

Substances

  • DNA-Binding Proteins
  • Luminescent Proteins
  • Rag2 protein, mouse
  • Recombinant Fusion Proteins
  • V(D)J recombination activating protein 2
  • Green Fluorescent Proteins