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

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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain / embryology
  • Brain / metabolism
  • Cell Death
  • Cell Line
  • Cell Proliferation
  • Chromosomal Proteins, Non-Histone
  • Embryo Loss / genetics
  • Embryo Loss / metabolism
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / embryology
  • Embryo, Mammalian / metabolism
  • Female
  • Fibroblasts
  • Gene Expression Regulation, Developmental*
  • Mice
  • Mice, Knockout
  • Mutation / genetics
  • Phenotype
  • Placenta / metabolism
  • Protein-Serine-Threonine Kinases / deficiency
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Transcription Factors

Substances

  • Brd2 protein, mouse
  • Chromosomal Proteins, Non-Histone
  • Transcription Factors
  • Protein-Serine-Threonine Kinases