The mifepristone-inducible gene regulatory system in mouse models of disease and gene therapy.

The mifepristone (Mfp)-inducible gene regulatory system is designed to allow control of the spatiotemporal expression of transgenes in vivo in a ligand-dependent manner. This regulatory system is composed of two components: (1) a chimeric transactivator protein that activates transgene transcription only in the presence of the progesterone antagonist Mfp, and (2) a target transgene placed in the context of a promoter which is responsive only to the Mfp-bound chimeric transactivator. Incorporation of the components of the Mfp-inducible gene regulatory system into transgenic mice has resulted in the establishment of several novel, Mfp-dependent models of disease. Similarly, adaptation of the Mfp-inducible system for use in gene knockout models has resulted in the development of new gene ablation technology which is both tissue-specific and Mfp-dependent. Additionally, the Mfp-inducible gene regulatory system has been used in animal experiments involving somatic gene therapy, where it has shown considerable promise in the regulation of both reporter and therapeutic gene expression. This review focuses on recent application of the Mfp-inducible system to transgenic models, gene knockout models, and somatic gene therapy experiments. In so doing, it demonstrates the considerable promise that future use of this system holds for better understanding and treatment of human disease.