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
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Animals, Genetically Modified
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Cell Lineage
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Cell Transformation, Neoplastic*
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Clone Cells
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DNA-Binding Proteins / genetics
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Disease Models, Animal*
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Female
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Fertilization in Vitro
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Gene Expression Profiling
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Genes, myc*
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Green Fluorescent Proteins
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Kidney / pathology
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Leukemia-Lymphoma, Adult T-Cell* / genetics
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Leukemia-Lymphoma, Adult T-Cell* / pathology
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Leukemic Infiltration
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Luminescent Proteins / metabolism
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Male
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Mice
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Mutation
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Neoplasm Transplantation
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Olfactory Bulb / pathology
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Promoter Regions, Genetic
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Recombinant Fusion Proteins / metabolism
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Spleen / pathology
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T-Lymphocytes / immunology
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T-Lymphocytes / pathology*
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T-Lymphocytes / physiology
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Thymus Gland / pathology
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Transgenes
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Zebrafish* / embryology
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Zebrafish* / genetics
Substances
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DNA-Binding Proteins
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Luminescent Proteins
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Rag2 protein, mouse
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Recombinant Fusion Proteins
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V(D)J recombination activating protein 2
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Green Fluorescent Proteins