BRG1 deletion de-represses p53 pathways inducing cell cycle inhibition and apoptosis during peri-gastrulation (541.10)

BRG1, a catalytic subunit of the SWI/SNF ATPase chromatin-remodeling complex, plays a vital role in gene regulation and tumorigenesis. Germline SWI/SNF function loss results in early embryonic lethality at approximately E3.5 in the mouse. BRG1 necessity during development beyond the pre-implantation stage, however, has not been defined. The myriad temporal genomic changes during development require chromatin remodeling to facilitate differential gene expression. We hypothesized that BRG1 deficiency during post-implantation development will cause gastrulation failure. Using a tamoxifen inducible conditional mouse model, we show that BRG1 ablation beginning at gastrulation results in arrested growth and early embryonic death. Mutant embryos failed to grow; histologic analysis revealed several developmental defects such as lack of normal cardiac structure and disrupted neural fold architecture. Immunohistochemistry analysis revealed aberrant expression of cell cycle and apoptosis marker proteins in BRG1 muta...