ZFIN ID: ZDB-PUB-050419-1
Cre/lox-regulated transgenic zebrafish model with conditional myc-induced T cell acute lymphoblastic leukemia
Langenau, D.M., Feng, H., Berghmans, S., Kanki, J.P., Kutok, J.L., and Look, A.T.
Date: 2005
Source: Proceedings of the National Academy of Sciences of the United States of America   102(17): 6068-6073 (Journal)
Registered Authors: Feng, Hui, Kanki, John, Langenau, David, Look, A. Thomas
Keywords: lymphoma; tal1/scl; lmo2
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • DNA-Binding Proteins/genetics
  • Extracellular Matrix Proteins/metabolism
  • Genes, myc*
  • Genetic Markers
  • Green Fluorescent Proteins/genetics*
  • Humans
  • Integrases/metabolism*
  • Leukemia-Lymphoma, Adult T-Cell/genetics*
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins
  • Protein-Lysine 6-Oxidase/metabolism
  • Zebrafish/genetics
PubMed: 15827121 Full text @ Proc. Natl. Acad. Sci. USA
We have created a stable transgenic rag2-EGFP-mMyc zebrafish line that develops GFP-labeled T cell acute lymphoblastic leukemia (T-ALL), allowing visualization of the onset and spread of this disease. Here, we show that leukemias from this transgenic line are highly penetrant and render animals moribund by 80.7 +/- 17.6 days of life (+/-1 SD, range = 50-158 days). These T cell leukemias are clonally aneuploid, can be transplanted into irradiated recipient fish, and express the zebrafish orthologues of the human T-ALL oncogenes tal1/scl and lmo2, thus providing an animal model for the most prevalent molecular subgroup of human T-ALL. Because T-ALL develops very rapidly in rag2-EGFP-mMyc transgenic fish (in which "mMyc" represents mouse c-Myc), this line can only be maintained by in vitro fertilization. Thus, we have created a conditional transgene in which the EGFP-mMyc oncogene is preceded by a loxed dsRED2 gene and have generated stable rag2-loxP-dsRED2-loxP-EGFP-mMyc transgenic zebrafish lines, which have red fluorescent thymocytes and do not develop leukemia. Transgenic progeny from one of these lines can be induced to develop T-ALL by injecting Cre RNA into one-cell-stage embryos, demonstrating the utility of the Cre/lox system in the zebrafish and providing an essential step in preparing this model for chemical and genetic screens designed to identify modifiers of Myc-induced T-ALL.