title: Mice lacking Dad1, the defender against apoptotic death-1, express abnormal N-linked glycoproteins and undergo increased embryonic apoptosis.
abstract: 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.
authors.affiliation: Division of Immunology and Cancer Research Laboratory, Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720-3200, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Hong
authors.forename: M
authors.initials: M
authors.lastname: Flannery
authors.forename: S N
authors.initials: SN
authors.lastname: Hsieh
authors.forename: D
authors.initials: D
authors.lastname: Cado
authors.forename: R
authors.initials: R
authors.lastname: Pedersen
authors.forename: A
authors.initials: A
authors.lastname: Winoto
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D029742:Caenorhabditis elegans Proteins; D006224:Cricetinae; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000235:genetics* / Q000502:physiology*; D006031:Glycosylation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D011247:Pregnancy; D012097:Repressor Proteins / Q000235:genetics* / Q000502:physiology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D029742:Caenorhabditis elegans Proteins; C096021:Dad-1 protein, C elegans; D006023:Glycoproteins; D012097:Repressor Proteins