Table 2. Phenotypes of mice with modifications at the Mdm2 and Mdmx loci.
Tissue | Genotype | p53 regulation strategy* | Phenotype‡ | Refs |
---|---|---|---|---|
CNS | Mdm2-/- | Nestin-Cre;Trp53LSL/- | Embryonic lethal; apoptosis | 24 |
Mdmx-/- | Nestin-Cre;Trp53LSL/- | Apoptosis and arrest | ||
Mdm2FM/FM | Nestin-Cre | Embryonic lethal; apoptosis | 109 | |
MdmxFX/FX | Nestin-Cre | Embryonic lethal; apoptosis and arrest | ||
Mdm2-/- | Trp53ER/- | No effect | 81 | |
Mdmx-/- | Trp53ER/- | Apoptosis only in SVZ | ||
Intestine | Mdm2FM/FM | Villin-Cre | Apoptosis | 164 |
MdmxFX/FX | Villin-Cre | Apoptosis in proliferating cells | 165 | |
Mdm2-/- | Trp53ER/- | Apoptosis | 81 | |
Mdmx-/- | Trp53ER/- | Apoptosis | 85 | |
Smooth muscle | Mdm2FM/FM | Sm22-CreERT2 | Cell death | 166 |
MdmxFX/FX | Sm22-CreERT2 | No effect | ||
Erythrocyte | Mdm2lox/lox | EporGFP-Cre/+ | Embryonic lethal; apoptosis | 167 |
Mdmxlox/lox | EporGFP-Cre/+ | Arrest only in fetal erythropoiesis | ||
Heart | Mdm2FM/- | Myhc-Cre | Embryonic lethal; apoptosis | 168 |
MdmxFX/- | Myhc-Cre | Apoptosis | 169 | |
Mdm2-/- | Trp53ER/- | No effect | 81 | |
Mdmx-/- | Trp53ER/- | No effect | 85 | |
Thymus and spleen | Mdm2-/- | Trp53ER/- | Apoptosis | 81 |
Mdmx-/- | Trp53ER/- | Apoptosis | 85 | |
Testis | Mdm2-/- | Trp53ER/- | Arrest | 81 |
Mdmx-/- | Trp53ER/- | Not reported | 85 | |
Lung, kidney and liver | Mdm2-/- | Trp53ER/- | No effect | 81 |
Mdmx-/- | Trp53ER/- | No effect | 85 |
CNS, central nervous system; Epor, erythropoietin receptor; FM, floxed Mdm2 allele; FX, floxed Mdmx allele; GFP, green fluorescent protein; Myhc, myosin heavy chain; Sm22, smooth muscle protein 22 (also known as transgelin); SVZ, subventricular zone.
Knockout of MDM2 or MDMX is embryonic lethal, and therefore either MDM knockout or p53 expression must be rendered conditional. This is usually achieved using Cre-mediated recombination. Note that the Trp53LSL and Trp53ER systems are to some extent ‘leaky’. Thus, adult animals can only be obtained by reducing Trp53 to hemizygosity.
Phenotype is for the adult tissue, except where the knockout was embryonic lethal.