Deletion of Dad1 in mice induces an apoptosis-associated embryonic death.
Dad1 is a putative anti-apoptosis gene identified in several distantly related organisms. Expression of Dad1 in transfected cells inhibits apoptosis in vitro. To determine whether Dad1 has a similar function in vivo, we used gene targeting to delete Dad1. Heterozygous adult mice (+/-) show no obvious phenotype or abnormalities, but genotype analysis of over 100 offspring from heterozygous matings detected no weanling, homozygous Dad1 null (-/-) mice. Subsequent analysis of embryos from heterozygous matings detected Dad1 null (-/-) embryos at E3.5 but no later, suggesting Dad1 is required for development beyond the late blastocyst stage. Increased levels of apoptosis were observed in cultured embryos lacking a functional copy of the gene, consistent with an anti-apoptotic role for Dad1.
Brewster
J L
JL
Stowers Institute for Medical Research, Kansas City, Missouri, USA. jbrewste@pepperdine.edu
Martin
S L
SL
Toms
J
J
Goss
D
D
Wang
K
K
Zachrone
K
K
Davis
A
A
Carlson
G
G
Hood
L
L
Coffin
J D
JD
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D020964:Embryo Loss / Q000235:genetics*; D005314:Embryonic and Fetal Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout
D051017:Apoptosis Regulatory Proteins; C489987:Dad1 protein, mouse; D008565:Membrane Proteins