title: Enforced expression of Simian virus 40 large T-antigen leads to testicular germ cell tumors in zebrafish.
abstract: 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.
authors.affiliation: Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20889, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Gill
authors.forename: Linda
authors.initials: L
authors.lastname: Lowe
authors.forename: Joan
authors.initials: J
authors.lastname: Nguyen
authors.forename: P Paul
authors.initials: PP
authors.lastname: Liu
authors.forename: Trevor
authors.initials: T
authors.lastname: Blake
authors.forename: Byrappa
authors.initials: B
authors.lastname: Venkatesh
authors.forename: Peter D
authors.initials: PD
authors.lastname: Aplan
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000957:Antigens, Viral, Tumor / Q000235:genetics*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000473:pathology*; D013539:Simian virus 40 / Q000235:genetics; D023741:Takifugu / Q000235:genetics; D013736:Testicular Neoplasms / Q000473:pathology*; D013737:Testis / Q000473:pathology; D015027:Zebrafish / Q000235:genetics
chemical_list: D000957:Antigens, Viral, Tumor