Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally.
Immunity
; 9(2): 267-76, 1998 Aug.
Article
in En
| MEDLINE
| ID: mdl-9729047
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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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cysteine Endopeptidases
/
Receptors, Tumor Necrosis Factor
/
Gene Targeting
/
Fas Receptor
/
Caspases
/
Fibroblasts
/
Genes, Lethal
Limits:
Animals
Language:
En
Journal:
Immunity
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
1998
Document type:
Article
Affiliation country:
Israel