Generation of tumors in transgenic mice expressing the SV40 T antigen under the control of ovarian-specific promoter 1.
Generation of tumors in transgenic mice expressing the SV40 T antigen under the control of ovarian-specific promoter 1.
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在卵巢特异性启动子 1 的控制下表达 SV40 T 抗原的转基因小鼠中肿瘤的产生。
DOI：
10.1016/s1071-5576(03)00073-x
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Vanderhyden,BarbaraC
中科院分区：
文献类型：
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作者：
Garson,Kenneth;Macdonald,Elizabeth;Dubé,Manon;Bao,Rudi;Hamilton,ThomasC;Vanderhyden,BarbaraC
目的：从卵巢组织特异性表达的大鼠逆转录病毒样元件转录本中克隆卵巢特异性启动子OSP-1，检测其在转基因小鼠中驱动卵巢特异性转录的能力。方法：将lacZ报告基因（OSP-lacZ）或SV 40病毒早期区域（OSP-TAg）置于OSP-1启动子的控制下，产生转基因小鼠。结果：经X-gal染色证实，lacZ基因在OSP-lacZ转基因小鼠卵巢中的表达仅限于卵巢，而在OSP-lacZ转基因小鼠卵巢中的表达仅限于卵巢。免疫组化检测显示lacZ主要表达于颗粒细胞和卵巢表面上皮细胞。OSP-TAg小鼠在多种组织中发生肿瘤，包括三只雌性创始小鼠中的两只中的单侧颗粒细胞肿瘤。在对侧卵巢的一只小鼠的颗粒细胞瘤，有轻微的变化，卵巢表面上皮细胞preneoplasia.Conclusions提示：虽然OSP-1启动子能够限制报告基因的表达，卵巢转基因小鼠，在OSP-TAg小鼠的TAg的表达导致卵巢肿瘤以及肿瘤在许多其他器官。这表明，尽管OSP-1启动子的转录主要发生在卵巢中，但该启动子在其他组织的细胞中充分渗漏，以允许它们通过SV 40 TAg的致瘤性转化。
Objective:The ovarian-specific promoter, OSP-1, which was cloned from the transcript of a rat retrovirus-like element specifically expressed in ovarian tissue, was tested for its ability to drive ovary-specific transcription in transgenic mice.Methods:Transgenic mice were generated with the lacZ reporter gene (OSP-lacZ) or the early region of SV40 virus (OSP-TAg) placed under the control of the OSP-1 promoter. OSP-lacZ and OSP-TAg transgenic animals were examined, respectively, for the expression of lacZ (OSP-lacZ) or the development of tumors (OSP-TAg).Results:The expression of lacZ in the resulting OSP-lacZ mice was restricted to the ovary as determined by X-gal staining of multiple organs. Immunohistochemical detection of β-galactosidase showed lacZ expression mainly in the granulosa cells and ovarian surface epithelial cells. OSP-TAg mice developed tumors in a variety of tissues, including unilateral granulosa cell tumors in two of three female founder mice. In the contralateral ovary of one mouse with a granulosa cell tumor, there wee alterations in the ovarian surface epithelial cells suggestive of preneoplasia.Conclusions:Although the OSP-1 promoter was able to restrict reporter gene expression to the ovary in transgenic mice, the expression of TAg in the OSP-TAg mice resulted in ovarian tumors as well as tumors in numerous other organs. This indicated that although transcription from the OSP-1 promoter occurs predominantly in the ovary, this promoter is sufficiently leaky in cells in other tissues to permit their tumorigenic conversion by SV40 TAg.