Temporal control of the Cre recombinase in transgenic mice by a tetracycline responsive promoter

Gene-targeted mice derived from embryonic stem cells are a useful tool to study gene function during development. However, if the mutation is embryonic lethal and the gene is deleted from the onset of development, later functions in adult animals cannot be studied. Recently, the bacterial Cre-loxP site-specific recombination system has successfully been used in transgenic animals to produce tissue-specific and temporal deletions [Gu et al. (1993) Cell, 73, 1155-1164; Gu et al, (1994) Science, 265, 103-106; Kuhn et al. (1995) Science, 269, 1427-1429]. We have evaluated the tetracycline responsive binary system [Gossen and Bujard (1992) Proc, Natl. Acad. Sci. USA, 89, 5547-5551] for its ability to transiently express the Cre recombinase in transgenic mice, In this system, a transactivator fusion protein composed of the tetracycline repressor (tetR) and the acidic domain of the herpes simplex viral protein 16 (VP16) can regulate the expression of the Cre gene from a promoter containing tet-operator (tetO) sequences. In the absence of tetracycline, the Cre gene is expressed and will induce site-specific recombination between two loxP sites. In the presence of tetracycline, the Cre gene will not be expressed and recombination will not occur.