Mice lacking Dad1, the defender against apoptotic death-1, express abnormal N-linked glycoproteins and undergo increased embryonic apoptosis

被引:58
作者
Hong, NA
Flannery, M
Hsieh, SN
Cado, D
Pedersen, R
Winoto, A [1 ]
机构
[1] Univ Calif Berkeley, Div Immunol, Berkeley, CA 94720 USA
[2] Univ Calif Berkeley, Canc Res Lab, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
[3] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, Reprod Genet Unit, San Francisco, CA 94143 USA
关键词
Dad1; glycosylation; apoptosis; Reichert's membrane; visceral endoderm; knockout;
D O I
10.1006/dbio.2000.9615
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Dad1 has been shown to play a role in preventing apoptotic cell death and in regulating levels of N-linked glycosylation in Saccharomyces cerevisiae and the BHK hamster cell line. To address the in vivo role of Dad1 in these processes during multicellular development, we have analyzed mice carrying a null allele for Dad1. Embryos homozygous for this mutation express abnormal N-glycosylated proteins and are developmentally delayed by embryonic day 7.5. Such mutants exhibit aberrant morphology, impaired mesodermal development, and increased levels of apoptosis in specific tissues. These defects culminate in homozygous embryos failing to turn the posterior axis and subsequent lethality by embryonic day 10.5. Thus, Dad1 is required for proper processing of N-linked glycoproteins and for certain cell survival in the mouse. (C) 2000 Academic Press.
引用
收藏
页码:76 / 84
页数:9
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