TY - JOUR
T1 - Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally
AU - Varfolomeev, Eugene E.
AU - Schuchmann, Marcus
AU - Luria, Victor
AU - Chiannilkulchai, Nuchanard
AU - Beckmann, Jacques S.
AU - Mett, Igor L.
AU - Rebrikov, Denis
AU - Brodianski, Vadim M.
AU - Kemper, Oliver C.
AU - Kollet, Orit
AU - Lapidot, Tsvee
AU - Soffer, Dror
AU - Sobe, Tama
AU - Avraham, Karen B.
AU - Goncharov, Tanya
AU - Holtmann, Helmut
AU - Lonai, Peter
AU - Wallach, David
N1 - Funding Information:
We thank Ahuva Kniszinsky and Tatiana Burakova for assistance in the gene targeting experiments, Niv Tutka for animal care, Adela Dibman for assistance in tissue culture work, Dr. Rebecca Haffner-Krausz for assistance in whole-mount in situ hybridization, Esther Arman for useful advice in ES cell culture and selection, Yuti Chernajovsky for advice on establishment of SV40 transformed cell lines and use of retroviral expression vectors, Lucy Rowe for assistance with chromosomal mapping data, Francoise Gary for expert technical help, and Shirley Smith for editorial assistance. This work was supported in part by grants from Inter-Lab Ltd., Ness Ziona, Israel; Ares Trading S. A., Switzerland; and from the Israeli Ministry of Arts and Sciences (E. E. V., M. S., I. L. M., D. R., V. M. B., O. C. K., D. S., T. G., and D. W.); the Infrastructure Laboratory for Gene Targeting, established by the Israel Ministry of Science (V. L. and P. L.); the Israel Science Foundation, founded by the Israel Academy of Sciences and Humanities—Charles H. Revson Foundation (T. S. and K. B. A.); and the Association Francaise contre les Myopathies (N. C. and J. S. B.). M. S. is a recipient of a fellowship of the Deutsche Forschungsgemeinschaft.
PY - 1998/8
Y1 - 1998/8
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/0032143986
U2 - 10.1016/S1074-7613(00)80609-3
DO - 10.1016/S1074-7613(00)80609-3
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AN - SCOPUS:0032143986
SN - 1074-7613
VL - 9
SP - 267
EP - 276
JO - Immunity
JF - Immunity
IS - 2
ER -