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

Details

Serval ID
serval:BIB_6DB438C95608
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally
Journal
Immunity
Author(s)
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.
ISSN
1074-7613 (Print)
Publication state
Published
Issued date
08/1998
Volume
9
Number
2
Pages
267-76
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Aug
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.
Keywords
Animals Antigens, CD95/pharmacology/*physiology Caspase 8 Caspase 9 *Caspases Cell Death/drug effects/genetics Cells, Cultured/drug effects Cysteine Endopeptidases/*genetics/*physiology DNA, Complementary/genetics Fetal Death/genetics Fibroblasts/*cytology/drug effects/physiology *Gene Targeting Genes, Lethal/*genetics Gestational Age Mice Mice, Inbred C57BL Mice, Knockout/embryology Phenotype Receptors, Tumor Necrosis Factor/*physiology Receptors, Tumor Necrosis Factor, Member 25 Transcription, Genetic/genetics
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 17:18
Last modification date
20/08/2019 15:27
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