Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally

Eugene E. Varfolomeev, Marcus Schuchmann, Victor Luria, Nuchanard Chiannilkulchai, Jacques S. Beckmann, Igor L. Mett, Denis Rebrikov, Vadim M. Brodianski, Oliver C. Kemper, Orit Kollet, Tsvee Lapidot, Dror Soffer, Tama Sobe, Karen B. Avraham, Tanya Goncharov, Helmut Holtmann, Peter Lonai, David Wallach*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 IκBα 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.

Original languageEnglish
Pages (from-to)267-276
Number of pages10
JournalImmunity
Volume9
Issue number2
DOIs
StatePublished - Aug 1998

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