Hematopoietic perturbation in zebrafish expressing a tel-jak2a fusion
- Onnebo, S.M., Condron, M.M., McPhee, D.O., Lieschke, G.J., and Ward, A.C.
- Experimental hematology 33(2): 182-188 (Journal)
- Registered Authors
- Lieschke, Graham J., McPhee, Dora, Ward, Alister C.
- MeSH Terms
- Acute Disease
- Amino Acid Sequence
- Animals, Genetically Modified
- DNA-Binding Proteins/genetics*
- Disease Models, Animal
- Embryo, Nonmammalian/physiology
- Janus Kinase 2
- Leukemia, Myeloid/genetics*
- Peptide Fragments/chemistry
- Protein-Tyrosine Kinases/genetics*
- Proto-Oncogene Proteins/genetics*
- Proto-Oncogene Proteins c-ets
- Recombinant Fusion Proteins/metabolism
- Repressor Proteins/genetics*
- 15676212 Full text @ Exp. Hematol.
Onnebo, S.M., Condron, M.M., McPhee, D.O., Lieschke, G.J., and Ward, A.C. (2005) Hematopoietic perturbation in zebrafish expressing a tel-jak2a fusion. Experimental hematology. 33(2):182-188.
OBJECTIVE: Various TEL-JAK2 fusions have been identified in patients with lymphoblastic and myeloid leukemias that result in constitutive activation of the JAK2 kinase domain. Such fusions can mediate factor-independent growth of hematopoietic cell lines and induction of malignancy in mouse models. MATERIALS AND METHODS: To assess whether zebrafish could be utilized as a suitable model for the study of myeloid oncogenesis, we generated a zebrafish tel-jak2a fusion oncoprotein based on that seen in a case of chronic myeloid leukemia. This was transiently expressed in zebrafish embryos under the control of the spi1 promoter, which is strongly active in myeloid precursors. RESULTS: Visual, histological, and molecular analysis revealed disruption of normal embryonic hematopoiesis, including perturbation of the myeloid and erythroid lineages. CONCLUSION: These results indicate that the zebrafish tel-jak2a oncoprotein is functional, and suggest that this organism will be useful for the experimental study of myeloid malignancy.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes