Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
|
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hematopoietic system
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• hematopoietic stem and progenitor cells (HSPC) from irradiated mice transplanted into irradiated mice reconstitute the HSPC population exhibit a competitive disadvantage over HSPC from untreated mice compared with cells from similarly irradiated wild-type mice
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
|
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mortality/aging
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• homozygotes die between implantation and E6.5
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embryo
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• at E5.5, mutant embryos have formed an active site of implantation but contain few, if any, cells relative to wild-type embryos
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reproductive system
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• many empty decidua are observed between E6.5 and E10.5
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Allelic
Composition |
Mdm2tm1Glo/Mdm2+
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Genetic
Background |
involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
|
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mortality/aging
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• mice treated with ionizing radiation exhibit increased mortality compared with similarly treated wild-type mice
• male mice are more sensitive to treatment with ionizing radiation than female mice
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cellular
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• following transformation with c-myc and activated Ras oncogenes, mouse embryonic fibroblasts exhibit 33% fewer foci compared with wild-type cells
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homeostasis/metabolism
Allelic
Composition |
Mdm2tm1Glo/Mdm2+
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Genetic
Background |
involves: 129S7/SvEvBrd |
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
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pigmentation
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• mild hyperpigmentation detectable beginning around 4 - 6 months of age
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integument
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• mild hyperpigmentation detectable beginning around 4 - 6 months of age
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limbs/digits/tail
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• mild hyperpigmentation detectable beginning around 4 - 6 months of age
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|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Mdm2tm2.1Glo mutation
(1 available);
any
Mdm2 mutation
(54 available)
|
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|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Mdm2tm2Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
|
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cardiovascular system
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N |
• exhibit rescue of the heart lethality seen in conditional Mdm2 mice and have the same life span as single homozygous Trp53 mice
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|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Mdm2tm2.1Glo mutation
(1 available);
any
Mdm2 mutation
(54 available)
Tg(Myh6-cre)2182Mds mutation
(3 available)
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mortality/aging
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• all die by E13.5, with abnormalities evident at E9.5 but not E9
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growth/size/body
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• smaller than controls, probably due to lack of blood flow, however they develop to the correct developmental stage
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cardiovascular system
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• significant thinning of the myocardial layer in the ventricles
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• heart mass is smaller in E9.5 embryos and by E13.5, most homozygotes lack any visible signs of a heart
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• one of the E13.5 embryos that still has a heart shows abnormal trabeculation in the ventricle and abnormal ventricular wall structure
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• hearts fail to function properly as indicated by blood leaking outside the heart and the backup of blood in the atrium
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• decrease in blood flow that results in congestion and backup of blood in other organs
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• exhibit blood leaking outside the heart
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muscle
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• significant thinning of the myocardial layer in the ventricles
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embryo
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• smaller than controls, probably due to lack of blood flow, however they develop to the correct developmental stage
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cellular
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Mdm4Gt(VICTR20)7Lex mutation
(0 available);
any
Mdm4 mutation
(191 available)
Trp53tm3Wahl mutation
(0 available);
any
Trp53 mutation
(232 available)
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cellular
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• cell cycle arrest in irradiate MEFs is improved compared to Trp53 single homozygous MEFs but is still not as robust as in wild-type MEFs
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|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Mdm4tm1Glo mutation
(0 available);
any
Mdm4 mutation
(191 available)
Trp53tm1Tyj mutation
(12 available);
any
Trp53 mutation
(232 available)
|
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mortality/aging
|
N |
• mice are born in expected Mendelian ratios
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Trp53tm1Tyj mutation
(12 available);
any
Trp53 mutation
(232 available)
|
|
|
mortality/aging
|
N |
• mice exhibit normal mortality in response to treatment with ionizing radiation
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Trp53tm1Tyj mutation
(12 available);
any
Trp53 mutation
(232 available)
|
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embryo
|
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• no embryos are found at E8.5
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Trp53tm1Tyj mutation
(12 available);
any
Trp53 mutation
(232 available)
|
|
|
mortality/aging
|
N |
• mice are born in expected Mendelian ratios
|
Allelic
Composition |
Mdm2tm1Glo/Mdm2+
Trp53tm1.1Tldo/Trp53+
|
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Genetic
Background |
involves: 129S2/SvPas * 129S7/SvEvBrd * BALB/c * C57BL/6 |
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Trp53tm1.1Tldo mutation
(0 available);
any
Trp53 mutation
(232 available)
|
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mortality/aging
|
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• some die within 3 months
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hematopoietic system
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• decreased compared to Trp53tm1.1Tldo/+ mice
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cellular
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• decreased compared to Trp53tm1.1Tldo/+ mice
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Trp53tm1Tyj mutation
(12 available);
any
Trp53 mutation
(232 available)
|
|
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Trp53tm3Wahl mutation
(0 available);
any
Trp53 mutation
(232 available)
|
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cellular
|
|
• irradiation-induced cell cycle arrest is partially restored these MEFs compared to Trp53 single homozygous MEFs
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Trp53tm3Wahl mutation
(0 available);
any
Trp53 mutation
(232 available)
|
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mortality/aging
|
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• no double homozygous mice are found
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Trp53tm2Wahl mutation
(0 available);
any
Trp53 mutation
(232 available)
|
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mortality/aging
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• compared with Mdm2tm1Glo heterozygotes
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hematopoietic system
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• compared with Trp53tm2Wahl homozygotes
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• prior to and after irradiation compared with Trp53tm2Wahl homozygotes
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• prior to and after irradiation compared with Trp53tm2Wahl homozygotes
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• prior to and after irradiation compared with Trp53tm2Wahl homozygotes
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• severe in irradiated-mice
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skeleton
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• severe atrophic in irradiated-mice
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immune system
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• compared with Trp53tm2Wahl homozygotes
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• prior to and after irradiation compared with Trp53tm2Wahl homozygotes
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• severe in irradiated-mice
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homeostasis/metabolism
endocrine/exocrine glands
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• compared with Trp53tm2Wahl homozygotes
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Mdm4Gt(VICTR20)7Lex mutation
(0 available);
any
Mdm4 mutation
(191 available)
Trp53tm1Wahl mutation
(0 available);
any
Trp53 mutation
(232 available)
|
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cellular
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• presence of one copy of Mdm2 partially restores the arrest response of Trp53tm1Wahl; p21 protein levels are increased slightly more compared to homozygous Trp53tm1Wahl, Mdm2tm1Glo/+ or homozygous Trp53tm1Wahl, Mdm4/+ heterozygotes
|
Allelic
Composition |
Mdm2tm1Glo/Mdm2+
Mdm4tm1Glo/Mdm4+
|
|
Genetic
Background |
involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 |
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Mdm4tm1Glo mutation
(0 available);
any
Mdm4 mutation
(191 available)
|
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mortality/aging
|
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• no mice are present at weaning
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• fewer than expected mice are born
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hematopoietic system
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• mice exhibit decreased extramedullary hematopoiesis in the liver
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nervous system
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• the granule layer of the cerebellum is hypoplastic with defects in both the external granule layer and the internal granule layer
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• 10% to 20% of mice exhibit exencephaly associated with cleft palate, or other types of neural tube closure defects, such as kinked tails
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growth/size/body
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• 10% to 20% of mice exhibit exencephaly associated with cleft palate, or other types of neural tube closure defects, such as kinked tails
|
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• mice are smaller than normal at birth
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cellular
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• following transformation with c-myc and activated Ras oncogenes, mouse embryonic fibroblasts exhibit fewer foci compared with wild-type or single heterozygote cells
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renal/urinary system
craniofacial
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• 10% to 20% of mice exhibit exencephaly associated with cleft palate, or other types of neural tube closure defects, such as kinked tails
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limbs/digits/tail
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• 10% to 20% of mice exhibit exencephaly associated with cleft palate, or other types of neural tube closure defects, such as kinked tails
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immune system
embryo
digestive/alimentary system
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• 10% to 20% of mice exhibit exencephaly associated with cleft palate, or other types of neural tube closure defects, such as kinked tails
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integument
|
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• embryos are pale mid-gestation
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endocrine/exocrine glands
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Trp53tm2Glo mutation
(1 available);
any
Trp53 mutation
(232 available)
|
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hematopoietic system
|
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• bone marrow sections show hypocellularity indicative of aplastic anemia
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• bone marrow sections show hypocellularity indicative of aplastic anemia
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nervous system
|
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• distribution of Purkinje neurons is disorganized in the cerebellum
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Trp53tm1Adv mutation
(1 available);
any
Trp53 mutation
(232 available)
|
|
|
mortality/aging
|
|
• no embryos are found at E8.5
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Mdm4tm1Glo mutation
(0 available);
any
Mdm4 mutation
(191 available)
|
|
|
mortality/aging
|
N |
• mice are born in expected Mendelian ratios
|
hematopoietic system
|
|
• bone marrow sections show hypocellularity indicative of aplastic anemia
|
|
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• bone marrow sections show hypocellularity indicative of aplastic anemia
|
nervous system
|
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• distribution of Purkinje neurons is disorganized in the cerebellum
|
pigmentation
integument
limbs/digits/tail
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Mdm4tm2.1Glo mutation
(0 available);
any
Mdm4 mutation
(191 available)
|
|
|
pigmentation
|
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• starting in early postnatal development
|
integument
|
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• starting in early postnatal development
|
limbs/digits/tail
|
|
• starting in early postnatal development
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Trp53tm1Wahl mutation
(0 available);
any
Trp53 mutation
(232 available)
|
|
|
cellular
|
|
• presence of one copy of Mdm2 partially restores the arrest response of Trp53tm1Wahl; p21 protein levels are modestly increased from homozygous Trp53 mutant levels
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Trp53tm1Wahl mutation
(0 available);
any
Trp53 mutation
(232 available)
|
|
|
mortality/aging
|
|
• no double homozygotes survive to birth
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Trp53tm3.1Glo mutation
(0 available);
any
Trp53 mutation
(232 available)
|
|
|
mortality/aging
|
|
• no newborn mice are recovered
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Trp53tm1Glo mutation
(0 available);
any
Trp53 mutation
(232 available)
Trp53tm4Glo mutation
(0 available);
any
Trp53 mutation
(232 available)
|
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mortality/aging
growth/size/body
behavior/neurological
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Trp53tm1Glo mutation
(0 available);
any
Trp53 mutation
(232 available)
|
|
|
mortality/aging
|
|
• as in Mdm2tm1Glo homozygotes
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mdm2tm1Glo mutation
(0 available);
any
Mdm2 mutation
(54 available)
Trp53tm3.1Glo mutation
(0 available);
any
Trp53 mutation
(232 available)
Trp53tm4Glo mutation
(0 available);
any
Trp53 mutation
(232 available)
|
|
|
mortality/aging
|
N |
• lethality observed in Mdm2tm1Glo homozygotes is completely rescued with mice surviving beyond 5 weeks
|
Analysis Tools