Messing A, Chen H Y, Palmiter R D, Brinster R L
Nature. 1985;316(6027):461-3. doi: 10.1038/316461a0.
The ability to introduce foreign DNA into the genome of mice offers unique opportunities to produce new models of disease process. Recent experiments have shown that integration and expression of simian virus 40 (SV40) T antigen genes and the murine mammary tumour virus (MMTV)-myc genes in transgenic mice can lead to the development of neoplasia in a remarkably tissue-specific manner. In the case of SV40-bearing mice, tumours consistently develop in the choroid plexus. In the accompanying paper, we show that the 72-base pair (bp) enhancer in the SV40 genome is instrumental in directing tumorigenesis to the choroid plexus. However, when the enhancer is deleted from a construction also containing the metallothionein-human growth hormone fusion gene (SV delta e-MGH), an entirely new pattern of pathology results. The present report focuses on transgenic mice carrying this construct; they develop demyelinating peripheral neuropathies, hepatocellular carcinomas and islet cell adenomas.
将外源DNA导入小鼠基因组的能力为建立疾病过程的新模型提供了独特的机会。最近的实验表明,猿猴病毒40(SV40)T抗原基因以及鼠乳腺肿瘤病毒(MMTV)-myc基因在转基因小鼠中的整合和表达能够以一种显著的组织特异性方式导致肿瘤形成。在携带SV40的小鼠中,肿瘤总是在脉络丛中发生。在随附的论文中,我们表明SV40基因组中的72个碱基对(bp)增强子有助于将肿瘤发生导向脉络丛。然而,当从一个也包含金属硫蛋白-人生长激素融合基因(SV delta e-MGH)的构建体中删除该增强子时,会产生一种全新的病理模式。本报告聚焦于携带该构建体的转基因小鼠;它们会发展出脱髓鞘性周围神经病、肝细胞癌和胰岛细胞腺瘤。