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

Dad1 has been shown to play a role in preventing apoptotic cell death and i n regulating levels of N-linked glycosylation in Saccharomyces cerevisiae a nd 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 abnorm al N-glycosylated proteins and are developmentally delayed by embryonic day 7.5. Such mutants exhibit aberrant morphology, impaired mesodermal develop ment, and increased levels of apoptosis in specific tissues. These defects culminate in homozygous embryos failing to turn the posterior axis and subs equent lethality by embryonic day 10.5. Thus, Dad1 is required for proper p rocessing of N-linked glycoproteins and for certain cell survival in the mo use. (C) 2000 Academic Press.