Department of Pediatrics, UT Southwestern Medical Center, Dallas, Texas, USA.
Zebrafish. 2009 Dec;6(4):319-27. doi: 10.1089/zeb.2009.0613.
Germ cell tumors (GCTs) affect infants, children, and adults and are the most common cancer type in young men. Progress in understanding the molecular basis of GCTs has been hampered by a lack of suitable animal models. Here we report the identification of a zebrafish model of highly penetrant, heritable testicular GCT isolated as part of a forward genetic screen for cancer susceptibility genes. The mutant line develops spontaneous testicular tumors at a median age of 7 months, and pedigree analysis indicates dominant inheritance of the GCT susceptibility trait. The zebrafish model exhibits disruption of testicular tissue architecture and the accumulation of primitive, spermatogonial-like cells with loss of spermatocytic differentiation. Radiation treatment leads to apoptosis of the tumor cells and tumor regression. The GCT-susceptible line can serve as a model for understanding the mechanisms regulating germ cells in normal development and disease and as a platform investigating new therapeutic approaches for GCTs.
生殖细胞肿瘤 (GCTs) 可影响婴儿、儿童和成人，并且是年轻男性中最常见的癌症类型。由于缺乏合适的动物模型，对 GCT 分子基础的理解进展一直受到阻碍。在这里，我们报告了一种斑马鱼模型的鉴定，该模型具有高穿透性和遗传性的睾丸 GCT，是作为癌症易感性基因的正向遗传筛选的一部分而分离出来的。突变系在 7 个月的中位年龄时自发发展为睾丸肿瘤，系谱分析表明 GCT 易感性特征呈显性遗传。该斑马鱼模型表现出睾丸组织结构的破坏和原始精原细胞样细胞的积累，伴随着精母细胞分化的丧失。放射治疗导致肿瘤细胞凋亡和肿瘤消退。易感性 GCT 系可作为研究正常发育和疾病中调节生殖细胞的机制的模型，并可作为研究 GCT 新治疗方法的平台。
