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

EE Varfolomeev, M Schuchmann, V Luria… - Immunity, 1998 - cell.com
EE Varfolomeev, M Schuchmann, V Luria, N Chiannilkulchai, JS Beckmann, IL Mett…
Immunity, 1998cell.com
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 …
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.
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