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Dev Dyn. 2009 Apr;238(4):908-17. doi: 10.1002/dvdy.21911.

Double bromodomain-containing gene Brd2 is essential for embryonic development in mouse.

Author information

1
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.

Abstract

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.

PMID:
19301389
PMCID:
PMC2771124
DOI:
10.1002/dvdy.21911
[Indexed for MEDLINE]
Free PMC Article

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