Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally - PubMed (original) (raw)
doi: 10.1016/s1074-7613(00)80609-3.
M Schuchmann, V Luria, N Chiannilkulchai, J S Beckmann, I L Mett, D Rebrikov, V M Brodianski, O C Kemper, O Kollet, T Lapidot, D Soffer, T Sobe, K B Avraham, T Goncharov, H Holtmann, P Lonai, D Wallach
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- PMID: 9729047
- DOI: 10.1016/s1074-7613(00)80609-3
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Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally
E E Varfolomeev et al. Immunity. 1998 Aug.
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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.
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