Phenotypes Associated with This Genotype

Genotype
MGI:3576493

• Allelic Composition: Trp53^tm3.1Glo/Trp53⁺
• Genetic Background: B6.129S7-Trp53^tm3.1Glo

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

mortality/aging

premature death ( J:95318 , J:317504 )

• heterozygous mutants die between 150 to 750 days after birth, however this survival curve is no different from heterozygous Trp53 mice (J:95318)

• median survival for the combined population of both males and females is 499 days i.e., similar to that of mice heterozygous for both Trp53 ^tm3.1Glo and Pml^tm1Ppp (504 days) (J:317504)

• median survival is 515 days for male mice and 463 days for female mice (J:317504)

neoplasm

increased metastatic potential ( J:95318 )

• the osteosarcomas and carcinomas of heterozygous mutants metastasized when compared to heterozygous Trp53^tm1Tyj mice

increased lymphoma incidence ( J:95318 , J:317504 )

• 31.5% of heterozygous mutants developed lymphomas (J:95318)

• 52% of mice develop lymphomas (when expressed as a % of tumor type); 13% of mice develop two tumor types, lymphomas and sarcomas (J:317504)

• 44% of mice exhibit lymphomas when tumor incidence is evaluated per mouse, including those that succumb to EMH, and expressed as a % disease/total number of mice (J:317504)

• when tumors are segregated by gender, 50% of males and 38% of females exhibit lymphomas (expressed as a % disease/total number of mice) (J:317504)

increased T cell derived lymphoma incidence ( J:317504 )

• only ~10% of lymphoid tumors are T-cell lymphomas

increased B cell derived lymphoma incidence ( J:317504 )

• immunophenotyping of lymphocytes from terminally resected tumors showed that ~90% of lymphoid tumors are B-cell lymphomas

increased carcinoma incidence ( J:95318 , J:317504 , J:317504 )

• 15.5% of heterozygous mutants developed carcinomas, which are rare in homozygotes (J:95318)

• 4% of mice develop carcinomas (whether expressed as a % of tumor type or as a % disease/total number of mice) (J:317504)

♀ • when tumors are segregated by gender, 0% of males and 8% of females exhibit carcinomas (expressed as a % disease/total number of mice) (J:317504)

increased sarcoma incidence ( J:95318 , J:317504 )

• 53% of heterozygous mutants developed sarcomas (J:95318)

• 43% of mice develop sarcomas (when expressed as a % of tumor type); 13% of mice develop two tumor types, lymphomas and sarcomas (J:317504)

• 37% of mice exhibit sarcomas (when expressed as a % disease/total number of mice) (J:317504)

• when tumors are segregated by gender, 14% of males and 8% of females exhibit soft-tissue sarcomas (expressed as a % disease/total number of mice) (J:317504)

increased osteosarcoma incidence ( J:317504 )

• when tumors are segregated by gender, 14% of males and 38% of females exhibit osteosarcomas (expressed as a % disease/total number of mice)

cellular

abnormal cell cycle ( J:95318 )

• higher DNA synthesis in MEFs with cells continuing to synthesize DNA between days 6 and 10 of culture compared to wildtype or heterozygous or homozygous Trp53^tm1Tyj MEFs which reached a quiescent state at day 6 and did not reenter the cell cycle

decreased cellular sensitivity to gamma-irradiation ( J:95318 )

• irradiated E13.5 heterozygous embryos showed no evidence of apoptosis in the hypothalamus compared to wildtype and heterozygous Trp53^tm1Tyj mutants that showed a high number of apoptotic cells

increased fibroblast proliferation ( J:95318 )

• MEFs initially did not show any significant differences in growth rate but by day 4, grew more rapidly than wildtype or heterozygous or homozygous null Trp53^tm1Tyj MEFs and reached a much higher saturation density

hematopoietic system

increased T cell derived lymphoma incidence ( J:317504 )

• only ~10% of lymphoid tumors are T-cell lymphomas

hepatosplenomegaly ( J:317504 )

• mice exhibit pronounced hepatosplenomegaly

extramedullary hematopoiesis ( J:317504 )

• 41% mice exhibit extramedullary hematopoiesis (EMH), with no histological evidence of transformation to acute leukemia

• EMH is associated with peripheral blood leukocytosis and macrocytic anemia, indicative of a myeloproliferative/myelodysplastic overlap

• when segregated by gender, 43% of males and 31% of females exhibit EMH

macrocytic anemia ( J:317504 )

• mice with EMH exhibit macrocytic anemia

increased leukocyte cell number ( J:317504 )

• mice with EMH exhibit peripheral blood leukocytosis

immune system

increased T cell derived lymphoma incidence ( J:317504 )

• only ~10% of lymphoid tumors are T-cell lymphomas

hepatosplenomegaly ( J:317504 )

• mice exhibit pronounced hepatosplenomegaly

increased leukocyte cell number ( J:317504 )

• mice with EMH exhibit peripheral blood leukocytosis

liver/biliary system

hepatosplenomegaly ( J:317504 )

• mice exhibit pronounced hepatosplenomegaly

growth/size/body

decreased body weight ( J:317504 )

• average body weight is significantly lower than that in C57BL/6 wild-type controls

hepatosplenomegaly ( J:317504 )

• mice exhibit pronounced hepatosplenomegaly

skeleton

increased osteosarcoma incidence ( J:317504 )

• when tumors are segregated by gender, 14% of males and 38% of females exhibit osteosarcomas (expressed as a % disease/total number of mice)

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:317504 )

• only ~10% of lymphoid tumors are T-cell lymphomas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Li-Fraumeni syndrome		DOID:3012	OMIM:PS151623	J:95318