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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.

Pubmed ID: 19301389 RIS Download

Mesh terms: Animals | Brain | Cell Death | Cell Line | Cell Proliferation | Chromosomal Proteins, Non-Histone | Embryo Loss | Embryo, Mammalian | Female | Fibroblasts | Gene Expression Regulation, Developmental | Mice | Mice, Knockout | Mutation | Phenotype | Placenta | Protein-Serine-Threonine Kinases

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Associated grants

  • Agency: NINDS NIH HHS, Id: NS27941
  • Agency: NIDDK NIH HHS, Id: R01 DK031775
  • Agency: NIDDK NIH HHS, Id: R01 DK031775-24
  • Agency: NIGMS NIH HHS, Id: GM 081767
  • Agency: NIDDK NIH HHS, Id: DK31775
  • Agency: NINDS NIH HHS, Id: R01 NS027941-19S1
  • Agency: NINDS NIH HHS, Id: R01 NS027941
  • Agency: NIDDK NIH HHS, Id: T32 DK07647

Mouse Genome Informatics (Data, Gene Annotation)

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