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- Title
Generation of Tumors in Transgenic Mice Expressing the SV40 T Antigen Under the Control of Ovarian-Specific Promoter 1.
- Authors
Garson, Kenneth; Macdonald, Elizabeth; Dubé, Manon; Bao, Rudi; Hamilton, Thomas C.; Vanderhyden, Barbara C.
- Abstract
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.
- Publication
Reproductive Sciences, 2003, Vol 10, Issue 4, p244
- ISSN
1933-7191
- Publication type
Article
- DOI
10.1016/S1071-5576(03)00073-X