Apaf1 is required for mitochondrial pathways of apoptosis and brain development.
Apoptosis is essential for the precise regulation of cellular homeostasis and development. The role in vivo of Apaf1, a mammalian homolog of C. elegans CED-4, was investigated in gene-targeted Apaf1-/- mice. Apaf1-deficient mice exhibited reduced apoptosis in the brain and striking craniofacial abnormalities with hyperproliferation of neuronal cells. Apaf1-deficient cells were resistant to a variety of apoptotic stimuli, and the processing of Caspases 2, 3, and 8 was impaired. However, both Apaf1-/- thymocytes and activated T lymphocytes were sensitive to Fas-induced killing, showing that Fas-mediated apoptosis in these cells is independent of Apaf1. These data indicate that Apaf1 plays a central role in the common events of mitochondria-dependent apoptosis in most death pathways and that this role is critical for normal development.
Pubmed ID: 9753321 RIS Download
Animals | Antigens, CD95 | Apoptosis | Apoptotic Protease-Activating Factor 1 | Brain | Brain Chemistry | Caspase 2 | Caspase 3 | Caspase 8 | Caspase 9 | Caspases | Cells, Cultured | Cysteine Endopeptidases | Cytochrome c Group | Embryo, Mammalian | Enzyme Precursors | Fibroblasts | Gene Expression | Head | Membrane Potentials | Mice | Mice, Knockout | Mitochondria | Phenotype | Proteins | Skin Abnormalities | Stem Cells | T-Lymphocytes | Thymus Gland | Ultraviolet Rays