Abstract
Homozygous targeted disruption of the mouse Caspase 8 (Casp8) gene was found to be lethal in utero. The Caspase 8 null embryos exhibited impaired heart muscle development and congested accumulation of erythrocytes. Recovery of hematopoietic colony-forming cells from the embryos was very low. In fibroblast strains derived from these embryos, the TNF receptors, Fas/Apo1, and DR3 were able to activate the Jun N-terminal kinase and to trigger IkappaB alpha phosphorylation and degradation. They failed, however, to induce cell death, while doing so effectively in wild-type fibroblasts. These findings indicate that Caspase 8 plays a necessary and nonredundant role in death induction by several receptors of the TNF/NGF family and serves a vital role in embryonal development.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Caspase 8
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Caspase 9
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Caspases*
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Cell Death / drug effects
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Cell Death / genetics
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Cells, Cultured / drug effects
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Cysteine Endopeptidases / genetics*
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Cysteine Endopeptidases / physiology*
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DNA, Complementary / genetics
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Fetal Death / genetics
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Fibroblasts / cytology*
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Fibroblasts / drug effects
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Fibroblasts / physiology
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Gene Targeting*
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Genes, Lethal / genetics*
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Gestational Age
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Mice
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Mice, Inbred C57BL
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Mice, Knockout / embryology
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Phenotype
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Receptors, Tumor Necrosis Factor / physiology*
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Receptors, Tumor Necrosis Factor, Member 25
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Transcription, Genetic / genetics
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fas Receptor / pharmacology
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fas Receptor / physiology*
Substances
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DNA, Complementary
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Member 25
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Tnfrsf25 protein, mouse
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fas Receptor
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Casp8 protein, mouse
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Casp9 protein, mouse
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Caspase 8
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Caspase 9
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Caspases
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Cysteine Endopeptidases