Phenotypes associated with this allele

• Allele Symbol: Mdm4^tm2.1Glo
• Allele Name: targeted mutation 2.1, Guillermina Lozano
• Allele ID: MGI:3612474
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Mdm4^tm2.1Glo/Mdm4^tm2.1Glo	involves: 129S4/SvJaeSor * C57BL/6J	MGI:3616707
cn2	Mdm4^tm2Glo/Mdm4^tm2.1Glo Tg(Myh6-cre)2182Mds/0 Trp53^tm1Tyj/Trp53^tm1Brn	involves: 129P2/OlaHsd * 129S/Sv * C57BL/6J * FVB/N	MGI:5907135
cn3	Mdm4^tm2Glo/Mdm4^tm2.1Glo Tg(Myh6-cre)2182Mds/0 Trp53^tm1Tyj/Trp53^+	involves: 129S2/SvPas * 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6J * FVB/N	MGI:5907132
cn4	Mdm4^tm2Glo/Mdm4^tm2.1Glo Tg(Myh6-cre)2182Mds/0	involves: 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6J * FVB/N	MGI:3616711
cx5	Mdm4^tm2.1Glo/Mdm4^tm2.1Glo Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S2/SvPas * 129S4/SvJaeSor * C57BL/6J	MGI:3616708
cx6	Mdm2^tm1Glo/Mdm2^+ Mdm4^tm2.1Glo/Mdm4^+	involves: 129S7/SvEvBrd	MGI:5140383

Genotype
MGI:3616707

hm1

• Allelic Composition: Mdm4^tm2.1Glo/Mdm4^tm2.1Glo
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6J

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

mortality/aging

prenatal lethality, complete penetrance ( J:104114 )

• stage not specified, however at E9.5, all embryos are abnormal

Genotype
MGI:5907135

cn2

• Allelic Composition: Mdm4^tm2Glo/Mdm4^tm2.1Glo; Tg(Myh6-cre)2182Mds/0; Trp53^tm1Tyj/Trp53^tm1Brn
• Genetic Background: involves: 129P2/OlaHsd * 129S/Sv * C57BL/6J * FVB/N

mortality/aging

decreased tumor-free survival time ( J:137114 )

• mice die due to tumors not heart failure

extended life span ( J:137114 )

• mice show an extended mean survival of 403 days compared to compound heterozygous Mdm4^tm2Glo/Mdm4^tm2.1Glo conditional mutants

cardiovascular system

cardiovascular system phenotype ( J:137114 )

N • mice do not exhibit signs of heart failure such as edema and poor breathing and exhibit rescue of the dilated cardiomyopathy

neoplasm

increased tumor incidence ( J:137114 )

Genotype
MGI:5907132

cn3

• Allelic Composition: Mdm4^tm2Glo/Mdm4^tm2.1Glo; Tg(Myh6-cre)2182Mds/0; Trp53^tm1Tyj/Trp53⁺
• Genetic Background: involves: 129S2/SvPas * 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6J * FVB/N

mortality/aging

extended life span ( J:137114 )

• mice show an extended median survival of 274 days compared to compound heterozygous Mdm4^tm2Glo/Mdm4^tm2.1Glo conditional mutants

Genotype
MGI:3616711

cn4

• Allelic Composition: Mdm4^tm2Glo/Mdm4^tm2.1Glo; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6J * FVB/N

mortality/aging

premature death ( J:104114 , J:137114 )

• some mice die within 1 year for unknown reasons, however do not observe any embryonic lethality (J:104114)

• median survival of 208 and 243 days for males and females, respectively (J:137114)

• mice die as a result of heart failure (J:137114)

cellular

increased cardiomyocyte apoptosis ( J:137114 )

cardiovascular system

cardiovascular system phenotype ( J:104114 )

N • no abnormalities in embryonic hearts are seen

decreased myocardial fiber number ( J:137114 )

• hearts exhibit half the number of cardiomyocytes at 8 months of age

increased myocardial fiber size ( J:137114 )

• marker analysis indicates cardiomyocyte hypertrophy

enlarged heart ( J:137114 )

thin ventricular wall ( J:137114 )

• ventricular walls are thinner and hypertrophic

dilated heart ventricle ( J:137114 )

• all 4 chambers are dilated and paler than control hearts

cardiac fibrosis ( J:137114 )

dilated cardiomyopathy ( J:137114 )

• severe dilated cardiomyopathy

congestive heart failure ( J:137114 )

• by 8-10 months of age, most mice have swollen bodies, have difficulty moving, and are out of breath

homeostasis/metabolism

edema ( J:137114 )

• edema in the lung and/or abdomen

muscle

decreased myocardial fiber number ( J:137114 )

• hearts exhibit half the number of cardiomyocytes at 8 months of age

increased myocardial fiber size ( J:137114 )

• marker analysis indicates cardiomyocyte hypertrophy

dilated cardiomyopathy ( J:137114 )

• severe dilated cardiomyopathy

increased cardiomyocyte apoptosis ( J:137114 )

growth/size/body

enlarged heart ( J:137114 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:137114

Genotype
MGI:3616708

cx5

• Allelic Composition: Mdm4^tm2.1Glo/Mdm4^tm2.1Glo; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * 129S4/SvJaeSor * C57BL/6J

normal phenotype

no abnormal phenotype detected ( J:104114 )

• double homozygotes are viable and born at the expected ratio, exhibiting rescue of the embryonic lethality of single homozygous Mdm4 mice, however no further phenotypic analysis is reported

Genotype
MGI:5140383

cx6

• Allelic Composition: Mdm2^tm1Glo/Mdm2⁺; Mdm4^tm2.1Glo/Mdm4⁺
• Genetic Background: involves: 129S7/SvEvBrd

pigmentation

increased foot pad pigmentation ( J:174216 )

• starting in early postnatal development

integument

increased foot pad pigmentation ( J:174216 )

• starting in early postnatal development

limbs/digits/tail

increased foot pad pigmentation ( J:174216 )

• starting in early postnatal development