Double bromodomain-containing gene Brd2 is essential for embryonic development in mouse.
The BET subfamily of bromodomain-containing genes is characterized by the presence of two bromodomains and a unique ET domain at their carboxyl termini. Here, we show that the founding member of this subfamily, Brd2, is an essential gene by generating a mutant mouse line lacking Brd2 function. Homozygous Brd2 mutants are embryonic lethal, with most Brd2(-/-) embryos dying by embryonic day 11.5. Before death, the homozygous embryos were notably smaller and exhibited abnormalities in the neural tube where the gene is highly expressed. Brd2-deficient embryonic fibroblast cells were observed to proliferate more slowly than controls. Experiments to explore whether placental insufficiency could be a cause of the embryonic lethality showed that injecting diploid mutant embryonic stem cells into tetraploid wild-type blastocysts did not rescue the lethality; that is Brd2-deficient embryos could not be rescued by wild-type extraembryonic tissues. Furthermore, there were enhanced levels of cell death in Brd2-deficient embryos.
Shang
Enyuan
E
Division of Statistical Genetics, Department of Biostatistics, Mailman School of Public Health and Department of Psychiatry, Columbia University Medical Center, New York, New York 10032, USA.
Wang
Xiangyuan
X
Wen
Duancheng
D
Greenberg
David A
DA
Wolgemuth
Debra J
DJ
D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D016923:Cell Death; D002460:Cell Line; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone; D020964:Embryo Loss / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D005260:Female; D005347:Fibroblasts; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D010920:Placenta / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D000092468:Bromodomain Containing Proteins
D002868:Chromosomal Proteins, Non-Histone; D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors; C490844:Brd2 protein, mouse; D000092468:Bromodomain Containing Proteins