对小鼠半胱天冬酶8基因进行靶向破坏，可消除肿瘤坏死因子受体、Fas/Apo1和DR3诱导的细胞死亡，且在出生前是致死性的。

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

作者信息

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

机构信息

Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel.

出版信息

Immunity. 1998 Aug;9(2):267-76. doi: 10.1016/s1074-7613(00)80609-3.

DOI:10.1016/s1074-7613(00)80609-3

PMID: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.

摘要

小鼠半胱天冬酶8（Casp8）基因的纯合靶向破坏在子宫内被发现是致死性的。Casp8基因敲除胚胎表现出心肌发育受损和红细胞的充血性积聚。从这些胚胎中回收造血集落形成细胞的效率非常低。在源自这些胚胎的成纤维细胞系中，肿瘤坏死因子受体、Fas/Apo1和DR3能够激活Jun氨基末端激酶并触发IkappaBα的磷酸化和降解。然而，它们未能诱导细胞死亡，而在野生型成纤维细胞中则能有效诱导细胞死亡。这些发现表明，半胱天冬酶8在肿瘤坏死因子/神经生长因子家族的几种受体诱导的细胞死亡中发挥必要且不可替代的作用，并在胚胎发育中起至关重要的作用。