Nayernia K, Samani A A, Klaproth S, Engel W
Institute of Human Genetics, University of Göttingen, Gosslerstrasse 12d, Göttingen, 37073, Germany.
Cell Biol Int. 1998;22(6):437-43. doi: 10.1006/cbir.1998.0272.
Cell-type specific tumorigenesis can be induced in transgenic mice by the directed expression of simian virus 40 (SV 40) large tumour antigen (TAg). In an attempt to determine the susceptibility of haploid male germ cells to neoplastic transformation by this oncogene, transgenic mice were generated that harboured a chimeric gene composed of the SV40 T antigen genes fused to the 2.3-kb 5' flanking sequences of the rat proacrosin gene. It was previously shown that this regulatory sequence is able specifically to direct the expression of CAT reporter gene in male germ cells with the onset of translation in early haploid male germ cells. The transgene showed regulated expression in male germ cells. Although T antigen immunostaining was detected specifically in spermatids, no testicular pathology was observed. This indicates that spermatids show no susceptibility to transformation by oncogene TAg. However, in about 10% of animals of two independent transgenic lines, we could find non-testicular tumours in abdomen with a sarcoma-like structure in advanced age which showed SV40 TAg expression.
通过猿猴病毒40(SV 40)大肿瘤抗原(TAg)的定向表达,可在转基因小鼠中诱导细胞类型特异性肿瘤发生。为了确定单倍体雄性生殖细胞对这种致癌基因诱导的肿瘤转化的易感性,构建了转基因小鼠,其携带一个嵌合基因,该基因由SV40 T抗原基因与大鼠前顶体蛋白基因2.3 kb的5'侧翼序列融合而成。先前的研究表明,这种调控序列能够在早期单倍体雄性生殖细胞开始翻译时,特异性地指导CAT报告基因在雄性生殖细胞中的表达。转基因在雄性生殖细胞中呈现出受调控的表达。尽管在精子细胞中特异性检测到了T抗原免疫染色,但未观察到睾丸病理变化。这表明精子细胞对致癌基因TAg诱导的转化不敏感。然而,在两个独立转基因品系的约10%的动物中,我们在老年动物的腹部发现了具有肉瘤样结构的非睾丸肿瘤,这些肿瘤显示出SV40 TAg表达。