A TRANSGENIC MOUSE MODEL FOR TRILATERAL RETINOBLASTOMA
A TRANSGENIC MOUSE MODEL FOR TRILATERAL RETINOBLASTOMA
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DOI：
10.1001/archopht.1990.01070100101043
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发表时间：
1990-08-01
影响因子：
--
通讯作者：
ALBERT, DM
中科院分区：
文献类型：
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作者：
OBRIEN, JM;MARCUS, DM;ALBERT, DM
我们提出了一种小鼠三边视网膜母细胞瘤的模型。在转基因表达SV40T抗原的小鼠中观察到眼部视网膜母细胞瘤和中枢神经系统肿瘤。在这个模型中，一种已知与视网膜母细胞瘤基因产物(p105-Rb)结合的致癌蛋白在视网膜细胞中特异表达。所有携带这种基因改变的动物都会患上多灶性视网膜肿瘤。中脑肿瘤发生在15%的眼部荷瘤动物身上，发生在松果体水平的大脑含水层腹侧。眼部肿瘤和中枢神经系统肿瘤均可在杂合子后代中通过10代连续繁殖而遗传。视网膜肿瘤具有人类视网膜母细胞瘤的大体形态、侵袭性、光镜和电子显微镜特征以及免疫组织化学染色特征。未分化的中线中枢神经系统肿瘤的光镜和电子显微镜特征以及免疫细胞化学特征进一步与人类三边视网膜母细胞瘤相关。我们提出了视网膜母细胞瘤发生的另一种机制，即在面对完整的视网膜母细胞瘤基因座时，视网膜母细胞瘤蛋白的局部功能失活。
We present a murine model of trilateral retinoblastoma. Ocular retinobalstoma and central nervous system tumors are observed in a line of mice formed by the transgenic expression of SV40 T-antigen. An oncogenic protein known to bind to the retinoblastoma gene product (p105-Rb) is specifically expressed within retinal cells in this model. All animals that carry this genetic alteration develop multifocal retinal tumors. Midbrain tumors are observed in 15% of ocular tumor-bearing animals, and these arise ventral to the cerebral aquedcut at the level of the pineal gland. Both ocular and central nervous system neoplasma are heritable in heterozygous offspring through 10 sequential generations of breeding. Retinal tumors display the gross appearance, invasive properties, light and electron microscopic features, and immunohistochemical staining characteristics of human retinoblastoma. The light and electron microscopic characteristics as well as immunocytochemical features of undifferentiated midline central nervous system neoplasms further correlate with human trilateral retinoblastoma. We postulate an alternative mechanism of retinoblastoma tumorigenesis that involves functional inactivation of retinoblastoma protein locally in the face of an intact retioblastoma gene locus.