| Abstract | 第5-7页 |
| 摘要 | 第8-11页 |
| Abbreviation | 第11-12页 |
| Chapter Ⅰ Review:Basic Knowledge about p53: from discovery toregulation and function | 第12-36页 |
| 1.1 Introduction | 第13-14页 |
| 1.2 Introduction to p53 | 第14-18页 |
| 1.2.1 Discovery of p53 | 第14-15页 |
| 1.2.2 Structure of p53 | 第15-17页 |
| 1.2.3 p53 functions as the guardian of the genome | 第17-18页 |
| 1.3 Post-translational regulation of p53 | 第18-22页 |
| 1.3.1 Regulation of p53 activity by MDM2 and MDM4 | 第18-21页 |
| 1.3.2 Regulation of p53 activation upon stresses | 第21-22页 |
| 1.4 Transcriptional regulation of p53 | 第22-26页 |
| 1.4.1 p53 expression in vitro | 第22-23页 |
| 1.4.2 p53 expression in vivo | 第23-25页 |
| 1.4.3 Regulation of p53 promoter activity | 第25-26页 |
| Summary and prospective | 第26-28页 |
| References | 第28-36页 |
| Chapter Ⅱ Highly active of p53 gene promoter in proliferating cells | 第36-61页 |
| 2.1 Abstract | 第37-38页 |
| 2.2 Introduction | 第38-40页 |
| 2.3 Results | 第40-56页 |
| 2.3.1 Generation p53-reporter mouse models | 第40-42页 |
| 2.3.2 Beta-gal is highly expressed in proliferating compartments in tissues | 第42-43页 |
| 2.3.3 High level of p53 mRNA expression in cycling cells in vitro | 第43-45页 |
| 2.3.4 Robust activation of p53 pathway in cycling cells upon stress | 第45-46页 |
| 2.3.5 Higher p53 expression in proliferating compartments of tissues | 第46-48页 |
| 2.3.6 Specific accumulation of p53 protein in cycling cells upon stress | 第48-51页 |
| 2.3.7 Increased p53 gene promoter activity during liver regeneration | 第51-53页 |
| 2.3.8 Generation of mouse model possessing mutated E-box in p53 gene promoter with CRISPR/Cas9 technology | 第53-55页 |
| 2.3.9 Decreased p53 mRNA in E-box mutant embryos and MEFs | 第55-56页 |
| 2.4 Discussion | 第56-58页 |
| References | 第58-61页 |
| Chapter Ⅲ Happlo-insufficiency of MDM2 and MDM4-Mediated cellular competition during mammalianembryogenesis | 第61-94页 |
| 3.1 Abstract | 第62-63页 |
| 3.2 Introduction | 第63-65页 |
| 3.3 Results | 第65-87页 |
| 3.3.1 Normal embryogenesis of mice with haplo-insufficiency of Mdm2 and Mdm4 | 第65-67页 |
| 3.3.2 Mdm2~(+/-) Mdm4~(+/-) mice are viable but exhibit slightly developmental delay | 第67-70页 |
| 3.3.3 Adult mice tolerated to haplo-insufficiency of Mdm2 and Mdm4 | 第70-72页 |
| 3.3.4 Mdm2~(+/-) Mdm4~(+/-) cells were eliminated during pancreas development | 第72-75页 |
| 3.3.5 Normal histology and function of Ipf1-cre;Mdm2flox/+；Mdm4+/- pancreas | 第75-76页 |
| 3.3.6 Universal elimination of Mdm2~(+/-) Mdm4~(+/-) cells during embryogenesis | 第76-79页 |
| 3.3.7 Cell competition uncovered by clonal analysis with Tamoxifen-inducible Cre | 第79-81页 |
| 3.3.8 Cell competition uncovered during embryogenesis with EllA-cre | 第81-83页 |
| 3.3.9 Elimination of Mdm2~(+/-) Mdm4~(+/-) cells in adult mice | 第83-85页 |
| 3.3.10 Mimicking cell competition in culture system with conditional medium | 第85-87页 |
| 3.3.11 Model | 第87页 |
| 3.4 Discussion | 第87-90页 |
| References | 第90-94页 |
| Chapter Ⅳ Summary & Methods/materiais | 第94-108页 |
| 4.1 Summary | 第95-97页 |
| 4.2 Methods and materials | 第97-108页 |
| 4.2.1 Mice and animal care | 第97-98页 |
| 4.2.2 Genotyping | 第98页 |
| 4.2.3 X-gal staining | 第98-99页 |
| 4.2.4 MEFs isolation | 第99页 |
| 4.2.5 Cell culture | 第99-100页 |
| 4.2.6 BrdU incorporation | 第100-101页 |
| 4.2.7 Partial-hepatectomy induced liver regeneration | 第101页 |
| 4.2.8 Immuno-histochemistry | 第101-103页 |
| 4.2.9 Western blot | 第103-104页 |
| 4.2.10 Antibodies | 第104页 |
| 4.2.11 RNA and Q-PCR | 第104-106页 |
| 4.2.12 Statistical analysis | 第106页 |
| 4.2.13 Primers for Q-PCR | 第106-108页 |
| 致谢 | 第108-109页 |
| Publications | 第109-111页 |
