Abnormalities of developmental cell death in Dad1-deficient mice.
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.


CONCLUSIONS
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.
Nishii
K
K
Department of Developmental Molecular Anatomy, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan. kiyo@mailserver.med.kyushu-u.ac.jp
Tsuzuki
T
T
Kumai
M
M
Takeda
N
N
Koga
H
H
Aizawa
S
S
Nishimoto
T
T
Shibata
Y
Y
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001755:Blastocyst / Q000502:physiology*; D002478:Cells, Cultured; D003433:Crosses, Genetic; D005314:Embryonic and Fetal Development; D005121:Extremities / Q000196:embryology; D005260:Female; D017353:Gene Deletion; D018390:Gene Targeting; D006602:Hexosyltransferases; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D013576:Syndactyly / Q000235:genetics*; D013950:Thymus Gland / Q000473:pathology; D014166:Transferases / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C489987:Dad1 protein, mouse; D008565:Membrane Proteins; D014166:Transferases; D006602:Hexosyltransferases; C025620:dolichyl-diphosphooligosaccharide - protein glycotransferase