Phenotypes Associated with This Genotype

Genotype
MGI:3584474

• Allelic Composition: Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S2/SvPas

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:88120 , J:95316 )

• animals die by about 26 weeks (J:88120)

• mean life span is 4.4 months (J:95316)

decreased tumor-free survival time ( J:132597 )

• majority of mice (82%) die before 9 months of age, or are euthanized due to occurrence of obvious tumor mass

prenatal lethality, incomplete penetrance ( J:95316 )

• a slight decrease is seen in the number of females born

growth/size/body

cardiac hypertrophy ( J:120332 )

• increased hypertrophy as a result of transverse aortic restriction

nervous system

abnormal neuron differentiation ( J:102702 )

• 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

increased medulloblastoma incidence ( J:102702 )

• 13/19 (68%) of animals receiving 4 Gy radiation at P5 or 6 develop cerebellar tumors

neoplasm

increased tumor incidence ( J:95316 )

• 32% have multiple tumors

increased lymphoma incidence ( J:221224 )

• 3 of 10 mice develop lymphomas involving the spleen and lymph nodes

increased T cell derived lymphoma incidence ( J:88120 , J:95316 , J:221224 , J:251434 )

• 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)

• 6 of 10 mice develop thymic lymphomas (J:221224)

• mice present with thymic lymphoma at around 180 days of age (J:251434)

increased medulloblastoma incidence ( J:102702 )

• 13/19 (68%) of animals receiving 4 Gy radiation at P5 or 6 develop cerebellar tumors

increased hemangiosarcoma incidence ( J:95316 )

• the incidence of hemangiosarcomas is 32% compared to 62% in Trp53^tm1Tyj/Trp53^tm2.1Tyj mice

cellular

polyploidy ( J:109354 )

• after irradiation with UVC light, MEFs from null mice show higher levels of polyploidy than Trp53^tm2Xu homozygotes

abnormal cell cycle checkpoint function ( J:77907 , J:126920 )

• 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)

decreased cellular sensitivity to ultraviolet irradiation ( J:77907 )

• reduced sensitivity to UV-induced cell death in MEFs compared to wild-type cells

decreased T cell apoptosis ( J:109354 )

• thymocytes are essentially resistant to Trp53-mediated apoptosis

decreased thymocyte apoptosis ( J:126920 , J:158953 , J:195018 )

• rare following exposure to ionizing radiation (J:126920)

• in response to irradiation (J:158953)

• in irradiated thymocytes (J:195018)

decreased splenocyte apoptosis ( J:195018 )

• in irradiated spleen cells

abnormal neuron differentiation ( J:102702 )

• 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

increased fibroblast proliferation ( J:77907 )

• in MEFs

immune system

decreased T cell apoptosis ( J:109354 )

• thymocytes are essentially resistant to Trp53-mediated apoptosis

decreased thymocyte apoptosis ( J:126920 , J:158953 , J:195018 )

• rare following exposure to ionizing radiation (J:126920)

• in response to irradiation (J:158953)

• in irradiated thymocytes (J:195018)

decreased splenocyte apoptosis ( J:195018 )

• in irradiated spleen cells

cardiovascular system

increased angiogenesis ( J:120332 )

• increased number of microvessels form 2 weeks after transverse aortic constriction

cardiac hypertrophy ( J:120332 )

• increased hypertrophy as a result of transverse aortic restriction

abnormal cardiovascular system physiology ( J:120332 )

• better systolic function than control

hematopoietic system

decreased T cell apoptosis ( J:109354 )

• thymocytes are essentially resistant to Trp53-mediated apoptosis

decreased thymocyte apoptosis ( J:126920 , J:158953 , J:195018 )

• rare following exposure to ionizing radiation (J:126920)

• in response to irradiation (J:158953)

• in irradiated thymocytes (J:195018)

decreased splenocyte apoptosis ( J:195018 )

• in irradiated spleen cells

endocrine/exocrine glands

decreased thymocyte apoptosis ( J:126920 , J:158953 , J:195018 )

• rare following exposure to ionizing radiation (J:126920)

• in response to irradiation (J:158953)

• in irradiated thymocytes (J:195018)

increased T cell derived lymphoma incidence ( J:88120 , J:95316 , J:221224 , J:251434 )

• 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)

• 6 of 10 mice develop thymic lymphomas (J:221224)

• mice present with thymic lymphoma at around 180 days of age (J:251434)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Li-Fraumeni syndrome		DOID:3012	OMIM:PS151623	J:95316