CHARACTERIZATION OF MICE DEFICIENT IN INTERLEUKIN-1-BETA CONVERTING-ENZYME

Interleukin-1 beta converting enzyme (ICE) processes the inactive prol L-1 beta to the proinflammatory mature IL-1 beta. ICE belongs to a fam ily of cysteine proteases that have been implicated in apoptosis. To a ddress the biological functions of ICE, we generated ICE-deficient mic e through gene targeting technology. ICE-deficient mice developed norm ally, appeared healthy, and were fertile. Peritoneal macrophages from ICE-deficient mice underwent apoptosis normally upon ATP treatment. Th ymocytes from young ICE-deficient mice also underwent apoptosis when t riggered by dexamethasone, gamma irradiation, or aging. ICE-deficient mice had a major defect in the production of mature IL-1 beta and had impaired IL-1 alpha production on LPS stimulation in vitro and in vivo . ICE-deficient mice were resistant to LPS-induced endotoxic shock. (C ) 1997 Wiley-Liss, Inc.