ATR disruption leads to chromosomal fragmentation and early embryonic lethality.
Although a small decrease in survival and increase in tumor incidence was observed in ATR(+/-) mice, ATR(-/-) embryos die early in development, subsequent to the blastocyst stage and prior to 7.5 days p.c. In culture, ATR(-/-) blastocysts cells continue to cycle into mitosis for 2 days but subsequently fail to expand and die of caspase-dependent apoptosis. Importantly, caspase-independent chromosome breaks are observed in ATR(-/-) cells prior to widespread apoptosis, implying that apoptosis is caused by a loss of genomic integrity. These data show that ATR is essential for early embryonic development and must function in processes other than regulation of p53.
Pubmed ID: 10691732 RIS Download
Animals | Apoptosis | Ataxia Telangiectasia Mutated Proteins | BRCA1 Protein | BRCA2 Protein | Blastocyst | Caspases | Cell Cycle Proteins | Cell Transformation, Neoplastic | Chromosome Aberrations | DNA Repair | Fetal Death | Gene Expression Regulation, Developmental | Gene Targeting | Genotype | Mice | Mice, Inbred C57BL | Mice, Knockout | Mitosis | Neoplasm Proteins | Neoplasms, Experimental | Protein-Serine-Threonine Kinases | Transcription Factors