Mouse Genome Informatics
hm1
    Trp53tm3.1Glo/Trp53tm3.1Glo
B6.129S7-Trp53tm3.1Glo
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 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

tumorigenesis
• 70% of mice develop lymphomas
• 29% of mice develop sacromas

homeostasis/metabolism
• DNA synthesis rates for mouse fibroblast cells continue to synthesize DNA after 10 days in culture whereas MEFs from a Trp53tm1Tyj homozygote are quiescent at day 6

cellular
• DNA synthesis rates for mouse fibroblast cells continue to synthesize DNA after 10 days in culture whereas MEFs from a Trp53tm1Tyj 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 Trp53tm1Tyj homozygote


Mouse Genome Informatics
ht2
    Trp53tm3.1Glo/Trp53+
B6.129S7-Trp53tm3.1Glo
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• heterozygous mutants die between 150 to750 days after birth, however this survival curve is no different from heterozygous Trp53 mice

tumorigenesis
• the osteosarcomas and carcinomas of heterozygous mutants metastasized when compared to heterozygous Trp53tm1Tyj 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

cellular
• 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 Trp53tm1Tyj 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 Trp53tm1Tyj 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 Trp53tm1Tyj MEFs and reached a much higher saturation density

Mouse Models of Human Disease
OMIM IDRef(s)
Li-Fraumeni Syndrome 1; LFS1 151623 J:95318


Mouse Genome Informatics
ht3
    Trp53tm1Tyj/Trp53tm3.1Glo
involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice do not survive past 300 days compared to Trp53tm1Tyj heterozygotes and Trp53tm3.1Glo heterozygotes that live to 900 days


Mouse Genome Informatics
ht4
    Trp53tm3.1Glo/Trp53tm4Glo
involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• median survival is 160 days due to tumor development

tumorigenesis
• tumors exhibit interstitial inflammatory cells unlike in tumors from Trp53tm3.1Glo/Trp53tm4Glo Tg(CAG-cre/Esr1*)5Amc mice
• in 60% of mice (including T cell, diffuse, and large cell)
• in 37% of mice (including angiosarcoma, spindle-cell, and giant-cell)


Mouse Genome Informatics
cn5
    Trp53tm3.1Glo/Trp53tm4Glo
Tg(CAG-cre/Esr1*)5Amc/0

involves: 129S7/SvEvBrd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• tamoxifen-treated mice survive longer than Trp53tm3.1Glo/Trp53tm4Glo mice

tumorigenesis
• tamoxifen-treated lymphomas exhibit increased apoptosis response compared with tumors from Trp53tm1Glo/Trp53tm4Glo Tg(CAG-cre/Esr1*)5Amc mice
• 3 of 5 tamoxifen-treated lymphomas exhibit senescence unlike in tumors from Trp53tm1Glo/Trp53tm4Glo 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


Mouse Genome Informatics
cx6
    Mdm2tm3.1Glo/Mdm2tm3.1Glo
Trp53tm3.1Glo/Trp53+

B6.129S-Mdm2tm3.1Glo Trp53tm3.1Glo
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• overall survival is reduced relative to mice homozygous for Mdm2tm4.1Glo and heterozygous for Trp53 tm3.1Glo

cellular
• in the thymus following a low dose of IR radiation compared to mice homozygous for Mdm2tm4.1Glo and heterozygous for Trp53tm3.1Glo

tumorigenesis
• accelerated tumor onset relative to mice homozygous for Mdm2tm4.1Glo and heterozygous for Trp53 tm3.1Glo
• the tumor spectrum is also altered relative to mice homozygous for Mdm2tm4.1Glo and heterozygous for Trp53 tm3.1Glo
• mice develop multiple primary tumors
• salivary carcinoma in 1 mouse
• undefined carcinomas are also reported
• soft tissue sarcoma
• chondrosarcoma in 1 mouse
• squamous cell papilloma in 1 mouse


Mouse Genome Informatics
cx7
    Mdm2tm4.1Glo/Mdm2tm4.1Glo
Trp53tm3.1Glo/Trp53+

B6.129S-Mdm2tm4.1Glo Trp53tm3.1Glo
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• an undefined carcinoma is reported in 1 mouse
• undefined adenocarcinomas are reported
• soft tissue sarcoma


Mouse Genome Informatics
cx8
    Mdm4tm3.1Glo/Mdm4tm3.1Glo
Trp53tm3.1Glo/Trp53tm3.1Glo

involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• unlike mice homozygous the Mdm4 allele alone, double mutant mice are viable (J:174368)


Mouse Genome Informatics
cx9
    Mdm2tm1Glo/Mdm2tm1Glo
Trp53tm3.1Glo/Trp53+

involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• no newborn mice are recovered


Mouse Genome Informatics
cx10
    Mdm2tm1Glo/Mdm2tm1Glo
Trp53tm3.1Glo/Trp53tm4Glo

involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• lethality observed in Mdm2tm1Glo homozygotes is completely rescued with mice surviving beyond 5 weeks (J:171821)