Characterization of mice deficient in interleukin-1 beta converting enzyme.
Interleukin-1 beta converting enzyme (ICE) processes the inactive prolL-1 beta to the proinflammatory mature IL-1 beta. ICE belongs to a family of cysteine proteases that have been implicated in apoptosis. To address the biological functions of ICE, we generated ICE-deficient mice through gene targeting technology. ICE-deficient mice developed normally, appeared healthy, and were fertile. Peritoneal macrophages from ICE-deficient mice underwent apoptosis normally upon ATP treatment. Thymocytes from young ICE-deficient mice also underwent apoptosis when triggered 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.
Li
P
P
BASF Bioresearch Corporation, Worcester, Massachusetts 01605-4314, USA. li@biovax.dnet.basf-ag.de
Allen
H
H
Banerjee
S
S
Seshadri
T
T
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D020170:Caspase 1; D003546:Cysteine Endopeptidases / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005688:Galactosamine / Q000494:pharmacology; D005720:Gamma Rays; D006579:Heterozygote; D007375:Interleukin-1 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D010641:Phenotype; D011995:Recombination, Genetic; D012772:Shock, Septic / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects
D007375:Interleukin-1; D008070:Lipopolysaccharides; D005688:Galactosamine; D003907:Dexamethasone; D000255:Adenosine Triphosphate; D003546:Cysteine Endopeptidases; D020170:Caspase 1