Generation of tumors in transgenic mice expressing the SV40 T antigen under the control of ovarian-specific promoter 1

• Published in: Journal of the Society for Gynecologic Investigation Vol. 10; no. 4; p. 244
• Main Authors: Garson, Kenneth, Macdonald, Elizabeth, Dubé, Manon, Bao, Rudi, Hamilton, Thomas C, Vanderhyden, Barbara C
• Format: Journal Article
• Language: English
• Published: United States 01.05.2003
• Subjects: Animals; Antigens, Viral, Tumor - genetics; Antigens, Viral, Tumor - physiology; Disease Models, Animal; Female; Gene Expression Regulation, Neoplastic - genetics; Gene Expression Regulation, Neoplastic - physiology; Immunohistochemistry; Lac Operon - physiology; Male; Mice; Mice, Transgenic; Nucleic Acid Hybridization; Ovarian Neoplasms - genetics; Promoter Regions, Genetic - genetics; RNA, Messenger - chemistry; RNA, Messenger - genetics; Simian virus 40 - genetics; Simian virus 40 - physiology; Transcription, Genetic
• ISSN: 1071-5576
• DOI: 10.1016/S1071-55760300073-X

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. 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). 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 beta-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 were alterations in the ovarian surface epithelial cells suggestive of preneoplasia. 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.