Conditional Expression Of Simian Virus 40 T Antigen Leads To Regulatable Development Of The Tumor Model By The Tet-on System In Transgenic Mice

Conditional Expression of Simian Virus 40 T Antigen Leads to Regulatable Development of the Tumor Model by the Tet-on System in Transgenic miceMD candidate: Hong Zhu Supervisor: Hou Da LiConditional oncogene expression in transgenic mice is of interest for studying the oncoprotein requirements during tumorigenesis that can be induced to undergo growh arrest and enhance their differentiated functions. Both tetracycline-controlled transactivator(tTA) and reverse tTA(rtTA) of which tTA activiates transcription in the absence of doxycycline(Dox) and rtTA in the presence of Dox , respectively, have allowed temporal and spatial control over gene expression in transgenic mice, providing unique genetic models for the study of development process and high-order functions. Simian Virus 40 T antigen is a potent oncoprotein that can induce several types of tumors. SV40 T antigen acts as a potent growth stimulator by inactiving p53 and Rb tumor suppressor genes, leading to uncontrolled cellular proliferation and tumor formation.We constructed the tetracycline-induced Simian Virus 40 T antigen expression vector in the Tet-on system and expressed it in vitro by the transfection and selection of double-stable cell lines.Based on the tetracycline regulatory of the Tet-on system, we established a binary transgenic model in which the conditional expression of SV40 T antigen under the control of the rtTA-regulated promoter. Analyes of the founder 123# binary transgenic mice line for SV40 TAg revealed that the transgenes could be regulated in the brain and the thymus gland by administration of doxycycline. Mice with rtTA and SV40 TAg transgenes developed medulloblastoma that could be induced by continuous doxycycline administration. Our report demonstrates the value of this transgenic model in the studying the physiological function of the SV40 T antigen of interesting a specific manner.