LIGAND-INDUCIBLE AND LIVER-SPECIFIC TARGET GENE-EXPRESSION IN TRANSGENIC MICE

Transgenic mice have been used as models for tissue-specific gene regu lation and to examine the molecular and cellular effects of altered ex pression of specific genes in disease processes such as tumorigenesis. Because of the deleterious effects of constitutive expression of tran sgenes, which frequently result in prenatal or postnatal death, only a limited number of disease models have been established in transgenic mice. We report an inducible binary transactivation system that permit s the control of transgene expression in a tissue-specific and inducib le fashion in mice. In this system, transcription of the target transg ene is kept silent until turned on by the administration of an exogeno us compound. We also demonstrate that expression level of the target g ene can be induced three to four orders of magnitude and can be contro lled by the administrated compound in a dose-dependent manner.