Mdm4;Trp53

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Lifespan (days)
114.5
Phenotype
Mdm4 has p53-independent function in vivo
Lifespan comparisons
Double mutant Mdm4(Tg1);p53(KO) has a lifespan of 114.5 days, while single mutant p53(KO) has a lifespan of 118.0 days.
Citation
View abstract
Xiong S et al., 2017, The p53 inhibitor Mdm4 cooperates with multiple genetic lesions in tumourigenesis. J Pathol. 241(4):501-510 27925213 Click here to select all mutants from this PubMed ID in the graph
Abstract
The p53 inhibitor Mdm4 is present at high levels in multiple human cancers. Overexpression of Mdm4 in mice drives the spontaneous development of mostly lymphomas and sarcomas. In this study, we explored the ability of Mdm4 to cooperate with lesions in tumour development. The Mdm4 transgene contributed to mammary tumour development in a BALB/cJ background. High levels of Mdm4 enhanced tumour development in a mutant p53R172H heterozygous background, and reduced the need to lose the wild-type p53 allele, as compared with mice heterozygous only for the p53R172H mutation. Additionally, high levels of Mdm4 cooperated with an oncogenic K-ras mutation to drive lung tumourigenesis in vivo. Finally, we examined p53-independent functions of Mdm4 by studying the contribution of Mdm4 to tumour development in the absence of p53. Whereas the overall survival times of p53-null mice with and without the Mdm4 transgene were similar, male mice with both alterations showed significantly shorter survival than p53-null male mice, and showed differences in tumour spectrum, demonstrating a p53-independent function of Mdm4 in tumourigenesis. Furthermore, p53-null mice with the highest level of Mdm4 tended to have multiple tumours. Thus, a detailed analysis of Mdm4 transgenic mice in various genetic backgrounds shows synergy in tumour development in vivo. Mdm4 may thus serve as a therapeutic target in cancers. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Lifespan (days)
115.5
Phenotype
Mdm4 has p53-independent function in vivo
Lifespan comparisons
Double mutant Mdm4(Tg15);p53(KO) has a lifespan of 115.5 days, while single mutant p53(KO) has a lifespan of 118.0 days and single mutant Mdm4(Tg15) has a lifespan of 489.0 days.
Citation
View abstract
Xiong S et al., 2017, The p53 inhibitor Mdm4 cooperates with multiple genetic lesions in tumourigenesis. J Pathol. 241(4):501-510 27925213 Click here to select all mutants from this PubMed ID in the graph
Abstract
The p53 inhibitor Mdm4 is present at high levels in multiple human cancers. Overexpression of Mdm4 in mice drives the spontaneous development of mostly lymphomas and sarcomas. In this study, we explored the ability of Mdm4 to cooperate with lesions in tumour development. The Mdm4 transgene contributed to mammary tumour development in a BALB/cJ background. High levels of Mdm4 enhanced tumour development in a mutant p53R172H heterozygous background, and reduced the need to lose the wild-type p53 allele, as compared with mice heterozygous only for the p53R172H mutation. Additionally, high levels of Mdm4 cooperated with an oncogenic K-ras mutation to drive lung tumourigenesis in vivo. Finally, we examined p53-independent functions of Mdm4 by studying the contribution of Mdm4 to tumour development in the absence of p53. Whereas the overall survival times of p53-null mice with and without the Mdm4 transgene were similar, male mice with both alterations showed significantly shorter survival than p53-null male mice, and showed differences in tumour spectrum, demonstrating a p53-independent function of Mdm4 in tumourigenesis. Furthermore, p53-null mice with the highest level of Mdm4 tended to have multiple tumours. Thus, a detailed analysis of Mdm4 transgenic mice in various genetic backgrounds shows synergy in tumour development in vivo. Mdm4 may thus serve as a therapeutic target in cancers. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Lifespan (days)
98.0
Phenotype
When the survival data were segregated in a gender-specific manner, the median survival of Mdm4Tg15, p53-/- (n=15) male mice was significantly shorter than p53-/- male mice (n=25) (98 vs 130 days, p=0.0042), but the median survival of p53-/- female mice was similar to Mdm4Tg15, p53-/- female mice
Lifespan comparisons
Double mutant Mdm4(Tg15);p53(KO) has a lifespan of 98.0 days, while single mutant p53(KO) has a lifespan of 130.0 days and single mutant Mdm4(Tg15) has a lifespan of 489.0 days.
Citation
View abstract
Xiong S et al., 2017, The p53 inhibitor Mdm4 cooperates with multiple genetic lesions in tumourigenesis. J Pathol. 241(4):501-510 27925213 Click here to select all mutants from this PubMed ID in the graph
Abstract
The p53 inhibitor Mdm4 is present at high levels in multiple human cancers. Overexpression of Mdm4 in mice drives the spontaneous development of mostly lymphomas and sarcomas. In this study, we explored the ability of Mdm4 to cooperate with lesions in tumour development. The Mdm4 transgene contributed to mammary tumour development in a BALB/cJ background. High levels of Mdm4 enhanced tumour development in a mutant p53R172H heterozygous background, and reduced the need to lose the wild-type p53 allele, as compared with mice heterozygous only for the p53R172H mutation. Additionally, high levels of Mdm4 cooperated with an oncogenic K-ras mutation to drive lung tumourigenesis in vivo. Finally, we examined p53-independent functions of Mdm4 by studying the contribution of Mdm4 to tumour development in the absence of p53. Whereas the overall survival times of p53-null mice with and without the Mdm4 transgene were similar, male mice with both alterations showed significantly shorter survival than p53-null male mice, and showed differences in tumour spectrum, demonstrating a p53-independent function of Mdm4 in tumourigenesis. Furthermore, p53-null mice with the highest level of Mdm4 tended to have multiple tumours. Thus, a detailed analysis of Mdm4 transgenic mice in various genetic backgrounds shows synergy in tumour development in vivo. Mdm4 may thus serve as a therapeutic target in cancers. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Lifespan (days)
310.0
Phenotype
Overexpression of Mdm4 cooperates with p53R172H/+ in tumorigenesis with significant reduction of p53 LOH
Lifespan comparisons
Double mutant Mdm4(Tg15);p53(R172H/+) has a lifespan of 310.0 days, while single mutant p53(R172H/+) has a lifespan of 395.0 days and single mutant Mdm4(Tg15) has a lifespan of 489.0 days.
Citation
View abstract
Xiong S et al., 2017, The p53 inhibitor Mdm4 cooperates with multiple genetic lesions in tumourigenesis. J Pathol. 241(4):501-510 27925213 Click here to select all mutants from this PubMed ID in the graph
Abstract
The p53 inhibitor Mdm4 is present at high levels in multiple human cancers. Overexpression of Mdm4 in mice drives the spontaneous development of mostly lymphomas and sarcomas. In this study, we explored the ability of Mdm4 to cooperate with lesions in tumour development. The Mdm4 transgene contributed to mammary tumour development in a BALB/cJ background. High levels of Mdm4 enhanced tumour development in a mutant p53R172H heterozygous background, and reduced the need to lose the wild-type p53 allele, as compared with mice heterozygous only for the p53R172H mutation. Additionally, high levels of Mdm4 cooperated with an oncogenic K-ras mutation to drive lung tumourigenesis in vivo. Finally, we examined p53-independent functions of Mdm4 by studying the contribution of Mdm4 to tumour development in the absence of p53. Whereas the overall survival times of p53-null mice with and without the Mdm4 transgene were similar, male mice with both alterations showed significantly shorter survival than p53-null male mice, and showed differences in tumour spectrum, demonstrating a p53-independent function of Mdm4 in tumourigenesis. Furthermore, p53-null mice with the highest level of Mdm4 tended to have multiple tumours. Thus, a detailed analysis of Mdm4 transgenic mice in various genetic backgrounds shows synergy in tumour development in vivo. Mdm4 may thus serve as a therapeutic target in cancers. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Lifespan (days)
325.0
Phenotype
Overexpression of Mdm4 cooperates with p53R172H/+ in tumorigenesis with significant reduction of p53 LOH
Lifespan comparisons
Double mutant Mdm4(Tg6);p53(R172H/+) has a lifespan of 325.0 days, while single mutant p53(R172H/+) has a lifespan of 395.0 days and single mutant Mdm4(Tg6) has a lifespan of 538.0 days.
Citation
View abstract
Xiong S et al., 2017, The p53 inhibitor Mdm4 cooperates with multiple genetic lesions in tumourigenesis. J Pathol. 241(4):501-510 27925213 Click here to select all mutants from this PubMed ID in the graph
Abstract
The p53 inhibitor Mdm4 is present at high levels in multiple human cancers. Overexpression of Mdm4 in mice drives the spontaneous development of mostly lymphomas and sarcomas. In this study, we explored the ability of Mdm4 to cooperate with lesions in tumour development. The Mdm4 transgene contributed to mammary tumour development in a BALB/cJ background. High levels of Mdm4 enhanced tumour development in a mutant p53R172H heterozygous background, and reduced the need to lose the wild-type p53 allele, as compared with mice heterozygous only for the p53R172H mutation. Additionally, high levels of Mdm4 cooperated with an oncogenic K-ras mutation to drive lung tumourigenesis in vivo. Finally, we examined p53-independent functions of Mdm4 by studying the contribution of Mdm4 to tumour development in the absence of p53. Whereas the overall survival times of p53-null mice with and without the Mdm4 transgene were similar, male mice with both alterations showed significantly shorter survival than p53-null male mice, and showed differences in tumour spectrum, demonstrating a p53-independent function of Mdm4 in tumourigenesis. Furthermore, p53-null mice with the highest level of Mdm4 tended to have multiple tumours. Thus, a detailed analysis of Mdm4 transgenic mice in various genetic backgrounds shows synergy in tumour development in vivo. Mdm4 may thus serve as a therapeutic target in cancers. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Mdm4;Trp53

Genetic mutants with Mdm4, Trp53 alterations