Internal medicine

Biology

Apoptosis

Immunology

Programmed cell death

Cell biology

Cancer research

Genetics

Medicine

Genes to Cells

Background Dad1, the defender against apoptotic cell death, comprises the oligosaccharyltransferase complex and is well conserved among eukaryotes. In hamster BHK21‐derived tsBN7 cells, loss of Dad1 causes apoptosis which cannot be prevented by Bcl‐2. Results To determine the role of Dad1 function in vivo , we prepared by gene targeting, mice harbouring a disrupted Dad1 gene. Homozygous mutants died shortly after they were implanted with the characteristic features of apoptosis. In an in vitro blastocyst culture system, Dad1‐null cells displayed abnormalities which were comparable to those obtained in vivo . However, oligosaccharyltransferase activity was apparently retained even after the Dad1‐null cells were destined to die. Some live‐born heterozygous mutants displayed soft‐tissue syndactyly. Mild thymic hypoplasia was also indicated in heterozygotes. Conclusion These results suggest the involvement of the Dad1 gene in the acquisition of a common syndactyly phenotype, as well as in the control of programmed cell death during development.

Abnormalities of developmental cell death in Dad1‐deficient mice