Open AccessEnforced Expression of Simian Virus 40 Large T-Antigen Leads to Testicular Germ Cell Tumors in Zebrafish
Author(s) -
J.A. Gill,
Linda A. Lowe,
J. M. Nguyen,
P. Paul Liu,
Trevor Blake,
Byrappa Venkatesh,
Peter D. Aplan
Publication year - 2010
Publication title -
zebrafish
Language(s) - English
Resource type - Journals
eISSN - 1557-8542
pISSN - 1545-8547
DOI - 10.1089/zeb.2010.0663
Subject(s) - zebrafish , biology , cancer research , transgene , gene , genetics
Testicular germ cell tumors (TGCTs) are the most common malignancy in young men. However, there are few in vivo animal models that have been developed to study this disease. We have used the pufferfish (fugu) lymphocyte-specific protein tyrosine kinase (flck) promoter, which has been shown to enforce high-level expression in the testes of transgenic mice, to express Simian virus 40 large T-antigen in zebrafish testes. Zebrafish that express T-antigen develop TGCTs after a long latency of >1 year. Although overt TGCTs are only evident in 20% of the fish, occult TGCTs can be detected in 90% of the transgenic fish by 36 month of age. The TGCTs resemble the human disease in terms of morphology and gene expression pattern, and can be transplanted to healthy wild-type recipient fish. In addition, enforced expression of the zebrafish stem cell leukemia (scl) gene in the zebrafish testes also generated TGCTs in transgenic fish. These results demonstrate the feasibility of studying TGCTs in a model organism.