PHOTORECEPTOR DEGENERATION INDUCED BY THE EXPRESSION OF SIMIAN VIRUS-40 LARGE TUMOR-ANTIGEN IN THE RETINA OF TRANSGENIC MICE
PHOTORECEPTOR DEGENERATION INDUCED BY THE EXPRESSION OF SIMIAN VIRUS-40 LARGE TUMOR-ANTIGEN IN THE RETINA OF TRANSGENIC MICE
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DOI：
10.1073/pnas.89.4.1194
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发表时间：
1992-02-15
影响因子：
11.1
通讯作者：
BAEHR, W
中科院分区：
文献类型：
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作者：
ALUBAIDI, MR;HOLLYFIELD, JG;BAEHR, W
编码猿猴病毒40（SV 40）大肿瘤抗原（T抗原）的病毒癌基因的表达通常促进哺乳动物细胞中的肿瘤发生。为了产生在视杆光感受器中表达T抗原的转基因小鼠，产生了由与SV 40 T抗原的编码区融合的小鼠视蛋白启动子片段组成的嵌合构建体。T抗原在转基因视网膜中的表达开始于出生后发育的早期阶段，伴随着内源性视蛋白的表达。而不是诱导增生或肿瘤形成，T-抗原的表达引起了快速进展的感光细胞变性。退化是伴随着持续的DNA合成感光细胞，证明了掺入[H-3]胸苷和有丝分裂的数字在出生后第10天，一个阶段时，非转基因感光细胞有丝分裂后和静止的外观。虽然转基因感光细胞经历S期并进入有丝分裂，但T抗原表达的结果不是增殖和肿瘤发生，而是增殖和细胞死亡。
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 [H-3]thymidine and by the appearance of mitotic figures at postnatal day 10, a stage when nontransgenic photoreceptor cells are post-mitotic 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.