Conditional mutagenesis - Second generation knockout mice as models for internal diseases

Knockout Mice: The generation of knockout mice has largely improved our und erstanding of the function of a variety of gene products. Gene inactivation experiments in mice have yielded numerous animal models for human diseases , thereby expanding our understanding of the underlying pathophysiological mechanisms. The use of conventional knockout experiments is limited if the phenotyp of gene disruption results in embryonic letality. Conditional Mutagenesis: Conditional mutagenesis aims to overcome this limi tation by regional and temporal control of gene inactivation in mice. Cre-loxP System: The bacteriophage-enzyme Cre recognizes loxP-sites can be introduced into intron regions of a target gene and mice can be created car rying this functional, but loxP-marked gene. When crossed with transgenic m ice expressing the Cre-recombinase under control of a tissue-specific and/o r inducible promoter the gene will be inactivated in vivo in a timely and r egionally controlled fashion.