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A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes
1Department of Genetics, Case Western Reserve University, Cleveland, OH 44106, USA.
Molecular Cell
|February 13, 2001
Summary
Brahma-related gene 1 (Brg1) is essential for early mammalian development, as Brg1 null mutations cause embryonic lethality. This challenges the idea of functional redundancy in SWI/SNF chromatin remodelers.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- Mammalian SWI/SNF complexes are ATP-dependent chromatin remodelers.
- These complexes use either Brahma (Brm) or Brahma-related gene 1 (Brg1) catalytic subunits.
- Brm's dispensability suggested functional redundancy between Brm and Brg1.
Purpose of the Study:
- To investigate the functional necessity of Brg1 in mammalian development.
- To test the hypothesis of functional redundancy between Brm and Brg1.
Main Methods:
- Gene targeting to create a Brg1 null mutation in mice.
- Analysis of homozygous and heterozygous Brg1 mutant embryos.
- Blastocyst outgrowth studies to assess cell survival.
Main Results:
- Brg1 homozygous null mutants exhibit lethality during the periimplantation stage.
- Neither inner cell mass nor trophectoderm survived in Brg1 null blastocysts.
- Brg1 heterozygotes showed predispositions to exencephaly and tumors.
- Brg1 was determined not to be a general cell survival factor.
Conclusions:
- Biochemically similar SWI/SNF complexes have distinct developmental roles.
- Brg1 plays a critical, non-redundant role in early mammalian embryogenesis.
- Loss of Brg1 function has severe developmental consequences, including embryonic lethality and predisposition to specific birth defects and cancers.
