Mouse Genome Informatics
hm
    Trp53tm1Tyj/Trp53tm1Tyj
involves: 129S2/SvPas
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• animals die by about 26 weeks (J:88120)
• mean life span is 4.4 months (J:95316)
• majority of mice (82%) die before 9 months of age, or are euthanized due to occurrence of obvious tumor mass (J:132597)
• a slight decrease is seen in the number of females born

nervous system
• GNPs from mutants show ~50% levels of proliferation compared to Cdkn2c, Trp53-double null cells after 3 days in culture and levels of cells incorporating BrdU are still less in single mutants in tests where cells are stimulated with Shh after culture

tumorigenesis
• 32% have multiple tumors
• mice start to develop T cell malignancies at 14-16 weeks (J:88120)
• 66% of homozygotes display hematological malignancies, primarily T cell lymphomas (J:95316)
• 13/19 (68%) of animals receiving 4 Gy radiation at P5 or 6 develop cerebellar tumors
• the incidence of hemangiosarcomas is 32% compared to 62% in Trp53tm1Tyj/Trp53tm2.1Tyj mice

cellular
• after irradiation with UVC light, MEFs from null mice show higher levels of polyploidy than Trp53tm2Xu homozygotes
• gamma-irradiation fails to produce an increase in the relative number of cells in G1 compared to S phase (J:77907)
• mouse embryonic fibroblasts exposed to radiation fail to arrest at the G1/S transition unlike similarly treated wild-type cells (J:126920)
• thymocytes are essentially resistant to Trp53-mediated apoptosis
• rare following exposure to ionizing radiation (J:126920)
• in response to irradiation (J:158953)
• in irradiated thymocytes (J:195018)
• in irradiated spleen cells
• reduced sensitivity to UV-induced cell death in MEFs compared to wild-type cells
• GNPs from mutants show ~50% levels of proliferation compared to Cdkn2c, Trp53-double null cells after 3 days in culture and levels of cells incorporating BrdU are still less in single mutants in tests where cells are stimulated with Shh after culture

immune system
• thymocytes are essentially resistant to Trp53-mediated apoptosis
• rare following exposure to ionizing radiation (J:126920)
• in response to irradiation (J:158953)
• in irradiated thymocytes (J:195018)
• in irradiated spleen cells

cardiovascular system
• increased number of microvessels form 2 weeks after transverse aortic constriction
• increased hypertrophy as a result of transverse aortic restriction
• better systolic function than control

hematopoietic system
• thymocytes are essentially resistant to Trp53-mediated apoptosis
• rare following exposure to ionizing radiation (J:126920)
• in response to irradiation (J:158953)
• in irradiated thymocytes (J:195018)
• in irradiated spleen cells

Mouse Models of Human Disease
OMIM IDRef(s)
Li-Fraumeni Syndrome 1; LFS1 151623 J:95316