[Conditional mutagenesis--second generation knockout mice as models for internal diseases].

KNOCKOUT MICE: The generation of knockout mice has largely improved our understanding 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 limitation by regional and temporal control of gene inactivation in mice. CRE-LOXP SYSTEM: The bacteriophage-enzyme Cre recognizes loxP-sites in the genome and excises loxP-flanked DNA-regions. Using this system loxP-sites can be introduced into intron regions of a target gene and mice can be created carrying this functional, but loxP-marked gene. When crossed with transgenic mice expressing the Cre-recombinase under control of a tissue-specific and/or inducible promoter the gene will be inactivated in vivo in a timely and regionally controlled fashion.