Establishing murine embryonic stem cells for generation of transgenic mice featuring predictable and regulatable transgene expressionVon der Fakultät für Lebenswissenschaftender Technischen Universität Carolo-Wilhelminazu Braunschweigzur Erlangung des Grades einerDoktorin der Naturwissenschaften(Dr. rer. nat.)genehmigteD i s s e r t a t i o nvon Pamela Riemeraus Uelzen 1. Referent: Prof. Dr. Jürgen Wehland 2. Referent: Prof. Dr. Michael Steinerteingereicht am: 22.10.2007mündliche Prüfung (Disputation) am: 28.02.2008Druckjahr 2008Table of contents1 Introduction ..................................................................................................................... 11.1 Regulated transgene activity in mammalian cells and transgenic mice......................11.1.1 Tetracycline (tet) regulated gene expression ....................................................41.1.1.1 Modifications and improvements of the tet dependent transactivator ...............61.1.1.2 Application of tet dependent transgene expression (in transgenic mice) ...........71.1.1.3 Autoregulated, tet dependent expression..........................................................91.1.1.4 Expression characteristics of the autoregulated tet system..............................111.2 Methods for introducing transgenes in mice ...........................................................121.2.1 Homologous Recombination ........................................................