• homozygous mutants die between 50 to 250 days after birth, however this survival curve is no different from homozygous null Trp53 mice homozygous mutants die between 50 to 250 days after birth, however this survival curve is no different from homozygous null Trp53 mice

• 70% of mice develop lymphomas

• 29% of mice develop sacromas

• DNA synthesis rates for mouse fibroblast cells continue to synthesize DNA after 10 days in culture whereas MEFs from a Trp53^tm1Tyj homozygote are quiescent at day 6

• DNA synthesis rates for mouse fibroblast cells continue to synthesize DNA after 10 days in culture whereas MEFs from a Trp53^tm1Tyj homozygote are quiescent at day 6

• at day 4 of culture, mouse embryonic fibroblast (MEF)cells reach a higher saturation concentration than do MEFs from a Trp53^tm1Tyj homozygote

• heterozygous mutants die between 150 to750 days after birth, however this survival curve is no different from heterozygous Trp53 mice

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

• 31.5% of heterozygous mutants developed lymphomas

• 15.5% of heterozygous mutants developed carcinomas, which are rare in homozygotes

• 53% of heterozygous mutants developed sarcomas

• 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

• 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

• 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

• mice do not survive past 300 days compared to Trp53^tm1Tyj heterozygotes and Trp53^tm3.1Glo heterozygotes that live to 900 days

• median survival is 160 days due to tumor development

• tumors exhibit interstitial inflammatory cells unlike in tumors from Trp53^tm3.1Glo/Trp53^tm4Glo Tg(CAG-cre/Esr1*)5Amc mice

• in 60% of mice (including T cell, diffuse, and large cell)

• in 4% of mice

• in 37% of mice (including angiosarcoma, spindle-cell, and giant-cell)

• tamoxifen-treated mice survive longer than Trp53^tm3.1Glo/Trp53^tm4Glo mice

• tamoxifen-treated lymphomas exhibit increased apoptosis response compared with tumors from Trp53^tm1Glo/Trp53^tm4Glo Tg(CAG-cre/Esr1*)5Amc mice

• 3 of 5 tamoxifen-treated lymphomas exhibit senescence unlike in tumors from Trp53^tm1Glo/Trp53^tm4Glo Tg(CAG-cre/Esr1*)5Amc mice

• tamoxifen-treated angiosarcomas and lymphomas exhibit senescence

• tamoxifen-treated mice exhibit little to no tumor growth unlike in control mice

• overall survival is reduced relative to mice homozygous for Mdm2^tm4.1Glo and heterozygous for Trp53 ^tm3.1Glo

• in the thymus following a low dose of IR radiation compared to mice homozygous for Mdm2^tm4.1Glo and heterozygous for Trp53^tm3.1Glo

• accelerated tumor onset relative to mice homozygous for Mdm2^tm4.1Glo and heterozygous for Trp53 ^tm3.1Glo

• the tumor spectrum is also altered relative to mice homozygous for Mdm2^tm4.1Glo and heterozygous for Trp53 ^tm3.1Glo

• mice develop multiple primary tumors

• in 1 mouse

• in 1 mouse

• squamous cell papilloma in 1 mouse

• salivary carcinoma in 1 mouse

• undefined carcinomas are also reported

• in 1 mouse

• soft tissue sarcoma

• chondrosarcoma in 1 mouse

• ovarian

• in 1 mouse

• in 1 mouse

• an undefined carcinoma is reported in 1 mouse

• undefined adenocarcinomas are reported

• in 1 mouse

• soft tissue sarcoma

• unlike mice homozygous the Mdm4 allele alone, double mutant mice are viable (J:174368)

• no newborn mice are recovered

• lethality observed in Mdm2^tm1Glo homozygotes is completely rescued with mice surviving beyond 5 weeks (J:171821)