ABSTRACT
Molecular mechanisms of development and disease can be studied in transgenic animals. Controlling the spatial and temporal expression patterns of transgenes, however, is a prerequisite for the elucidation of gene function in the whole organism. From the several binary systems which have been established to permit conditional activation of transgenes, the tetracycline responsive expression system has been the most successful one in animals. Transgenic mice carrying a tetR/VP16 hybrid gene (tTA) under different promoters have been used to temporally activate several-thousand fold the expression of genes under the control of a promoter containing tetop sequences. The importance of tetracycline regulatable systems goes beyond their ability to direct temporal gene expression in the context of the whole animal. In combination with Cre/lox recombination tools it will facilitate the deletion of genes from the genome in specific cells and at specific timepoints. This approach is required to test the function of genes whose presence is critical for embryonic development.
