REGULATION OF CRE RECOMBINASE ACTIVITY BY MUTATED ESTROGEN-RECEPTOR LIGAND-BINDING DOMAINS

Ligand-dependent chimeric Cre recombinases are powerful tools to induc e specific DNA rearrangements in cultured cells and in mice. We report here the construction and characterization of a series of chimeric re combinases, each consisting of Cre fused to a mutated human oestrogen receptor (ER) ligand-binding domain (LED). Two new ligand-dependent re combinases which contain either the G400V/M543A/L544A or the G400V/L53 9A/L540A triple mutation of the human ER LED are efficiently induced b y the synthetic ER antagonists 4-hydroxytamoxifen (OHT) and ICI 182,78 0 (ICI), respectively, but are insensitive to 17 beta-oestradiol (E2). Both chimeric recombinases should be useful for efficient spatio-temp orally controlled site-directed somatic mutagenesis. (C) 1997 Academic Press.