Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally
- Varfolomeev, E. E.
- Schuchmann, M.
- Luria, V.
- Chiannilkulchai, N.
- Beckmann, J. S.
- Mett, I. L.
- Rebrikov, D.
- Brodianski, V. M.
- Kemper, O. C.
- Kollet, O.
- Lapidot, T.
- Soffer, D.
- Sobe, T.
- Avraham, K. B.
- Goncharov, T.
- Holtmann, H.
- Lonai, P.
- Wallach, D.
DOIAbstract
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 rol...
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