al-Ubaidi M R, Hollyfield J G, Overbeek P A, Baehr W
Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030.
Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1194-8. doi: 10.1073/pnas.89.4.1194.
Expression of the viral oncogene encoding the simian virus 40 (SV40) large tumor antigen (T antigen) typically promotes tumorigenesis in mammalian cells. To generate transgenic mice that express T antigen in rod photoreceptors, a chimeric construct consisting of a mouse opsin promoter fragment fused to the coding region of SV40 T antigen was generated. Expression of T antigen in the transgenic retina began at early stages of postnatal development concomitant with expression of endogenous opsin. Instead of inducing hyperplasia or tumor formation, T-antigen expression caused a rapidly progressing photoreceptor degeneration. The degeneration was accompanied by sustained DNA synthesis in photoreceptor cells, as evidenced by incorporation of [3H]thymidine and by the appearance of mitotic figures at postnatal day 10, a stage when nontransgenic photoreceptor cells are postmitotic and quiescent. Although transgenic photoreceptor cells undergo S phase and enter mitosis, the consequences of T-antigen expression are not proliferation and tumorigenesis but proliferation and cell death.
编码猿猴病毒40（SV40）大T抗原（T抗原）的病毒癌基因的表达通常会促进哺乳动物细胞的肿瘤发生。为了生成在视杆光感受器中表达T抗原的转基因小鼠，构建了一种嵌合构建体，该构建体由与SV40 T抗原编码区融合的小鼠视蛋白启动子片段组成。转基因视网膜中T抗原的表达在出生后发育的早期阶段开始，与内源性视蛋白的表达同时出现。T抗原的表达并未诱导增生或肿瘤形成，而是导致了快速进展的光感受器退化。这种退化伴随着光感受器细胞中持续的DNA合成，这通过[3H]胸腺嘧啶核苷的掺入以及出生后第10天有丝分裂图的出现得到证明，而在这个阶段非转基因光感受器细胞已停止有丝分裂且处于静止状态。尽管转基因光感受器细胞经历S期并进入有丝分裂，但T抗原表达的后果不是增殖和肿瘤发生，而是增殖和细胞死亡。
