APOPTOSIS OR RETINOBLASTOMA - ALTERNATIVE FATES OF PHOTORECEPTORS EXPRESSING THE HPV-16 E7 GENE IN THE PRESENCE OR ABSENCE OF P53
APOPTOSIS OR RETINOBLASTOMA - ALTERNATIVE FATES OF PHOTORECEPTORS EXPRESSING THE HPV-16 E7 GENE IN THE PRESENCE OR ABSENCE OF P53
复制标题
DOI：
10.1101/gad.8.11.1300
复制
发表时间：
1994-06-01
影响因子：
10.5
通讯作者：
WINDLE, JJ
中科院分区：
文献类型：
--
作者：
HOWES, KA;RANSOM, LN;WINDLE, JJ
以前利用间质视黄醇结合蛋白(IRBP)基因启动子将SV40T抗原的表达导向视网膜感光细胞，建立了转基因小鼠视网膜母细胞瘤模型。在光感受器的末端分化之前，这个基因就变得活跃起来。由于T抗原转化活性至少部分归因于视网膜母细胞瘤(PRB)和P53肿瘤抑制蛋白的失活，我们讨论了P53在小鼠视网膜母细胞瘤发展中的作用。在IRBP启动子的控制下，获得了表达HPV-16E7的转基因小鼠，以灭活光感受器中的pRb，同时保持P53的完整。这些小鼠的视网膜不是发展成视网膜母细胞瘤，而是由于光感受器细胞在发育过程中死亡而退化，而此时光感受器通常正在进行末端分化。死亡的细胞具有凋亡的组织学和超微结构特征，并含有片段化的DNA。在这个模型中，P53是诱导细胞凋亡所必需的，因为在P53缺失背景下表达E7的小鼠会发生视网膜肿瘤，而不是经历视网膜退化。
A transgenic mouse model for retinoblastoma was produced previously by directing SV40 T antigen expression to retinal photoreceptor cells using the promoter of the interstitial retinol-binding protein (IRBP) gene. This gene becomes active prior to the terminal differentiation of photoreceptors. Because T antigen-transforming activity is attributable, at least in part, to the inactivation of the retinoblastoma (pRb) and p53 tumor suppressor proteins, we addressed the role of p53 in the development of retinoblastoma in mice. Transgenic mice expressing HPV-16 E7 under the control of the IRBP promoter were generated to inactivate pRb in photoreceptors while leaving p53 intact. Rather than developing retinoblastomas, the retinas of these mice degenerate due to photoreceptor cell death at a time in development when photoreceptors are normally undergoing terminal differentiation. The dying cells exhibit the histological and ultrastructural features of apoptosis and contain fragmented DNA. p53 is required for the induction of apoptosis in this model, because mice expressing E7 in a p53 nullizygous background develop retinal tumors instead of undergoing retinal degeneration.