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PMID:23230510
| Citation |
Kawamata, M and Ochiya, T (2012) Two distinct knockout approaches highlight a critical role for p53 in rat development. Sci Rep 2:945 |
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| Abstract |
Gene targeting in embryonic stem cells (ESCs) has become the principal technology for generating knockout models. Although numerous studies have predicted that the disruption of p53 leads to increased developmental anomalies and malignancies, most p53 knockout mice develop normally. Therefore, the role of p53 in animal development was examined using rat knockout models. Conventionally generated homozygous KO males developed normally, whereas females rarely survived due to neural tube defects. Mutant chimeras generated via blastocyst injection with p53-null ESCs exhibited high rates of embryonic lethality in both sexes. This phenotype could be observed in one month by the use of zinc-finger nucleases. The p53-null ESCs were resistant to apoptosis and differentiation, and exhibited severe chromosome instabilities in the chimera-contributed cells, suggesting an essential role for p53 in maintaining ESC quality and genomic integrity. These results demonstrate that p53 functions as a guardian of embryogenesis in the rats. |
| Links |
PubMed PMC3517977 Online version:10.1038/srep00945 |
| Keywords |
Animals; Apoptosis; Blastocyst/cytology; Blastocyst/metabolism; Cell Differentiation; Cell Line; Chromosomal Instability; Embryonic Development; Embryonic Stem Cells/cytology; Embryonic Stem Cells/metabolism; Female; Gene Expression Profiling; Gene Knockout Techniques; Homozygote; Male; Models, Animal; Rats; Tumor Suppressor Protein p53/genetics; Tumor Suppressor Protein p53/metabolism |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0009790: embryo development |
ECO:0000315: |
P |
Figure 3c: Mutant chimeras were created through blastocyte injection. The p53-/ESC- chimeras were the least likely to develop to become neonates when compared to p53+/ESC+ and p53+/ESC- chimeras. Figure 3d: Of the injected chimeras, p53-/ESC- chimeras were the least likey to have normal body size at the end of embryo development when compared to p53+/ESC+ and p53+/ESC- chimera. |
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Notes
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