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.
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.
Authors: C Rampon; C H Jiang; H Dong; Y P Tang; D J Lockhart; P G Schultz; J Z Tsien; Y Hu Journal: Proc Natl Acad Sci U S A Date: 2000-11-07 Impact factor: 11.205
Authors: Subramaniam Jayanthi; Michael T McCoy; Genevieve Beauvais; Bruce Ladenheim; Kristi Gilmore; William Wood; Kevin Becker; Jean Lud Cadet Journal: PLoS One Date: 2009-06-30 Impact factor: 3.240
Authors: Stefan Knirr; Janette Gomos-Klein; Blanca E Andino; Faith Harrow; Karl F Erhard; Damian Kovalovsky; Derek B Sant'Angelo; Benjamin D Ortiz Journal: PLoS One Date: 2010-11-22 Impact factor: 3.240
Authors: Arnis Druka; Elena Potokina; Zewei Luo; Nicola Bonar; Ilze Druka; Ling Zhang; David F Marshall; Brian J Steffenson; Timothy J Close; Roger P Wise; Andris Kleinhofs; Robert W Williams; Michael J Kearsey; Robbie Waugh Journal: Theor Appl Genet Date: 2008-04-30 Impact factor: 5.699