PUBLICATION
Cre/lox-regulated transgenic zebrafish model with conditional myc-induced T cell acute lymphoblastic leukemia
- Authors
- Langenau, D.M., Feng, H., Berghmans, S., Kanki, J.P., Kutok, J.L., and Look, A.T.
- ID
- ZDB-PUB-050419-1
- 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
-
- Humans
- Protein-Lysine 6-Oxidase/metabolism
- Integrases/metabolism*
- Extracellular Matrix Proteins/metabolism
- Nuclear Proteins
- Genes, myc*
- Animals, Genetically Modified
- Mice
- Animals
- Green Fluorescent Proteins/genetics*
- DNA-Binding Proteins/genetics
- Genetic Markers
- Zebrafish/genetics
- Molecular Sequence Data
- Leukemia-Lymphoma, Adult T-Cell/genetics*
- PubMed
- 15827121 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Langenau, D.M., Feng, H., Berghmans, S., Kanki, J.P., Kutok, J.L., and Look, A.T. (2005) Cre/lox-regulated transgenic zebrafish model with conditional myc-induced T cell acute lymphoblastic leukemia. Proceedings of the National Academy of Sciences of the United States of America. 102(17):6068-6073.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping