Phenotypes associated with this allele

• Allele Symbol: Ep300^tm1Dli
• Allele Name: targeted mutation 1, David Livingston
• Allele ID: MGI:1858020
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ep300^tm1Dli/Ep300^tm1Dli	either: 129S4/SvJae or (involves: 129S4/SvJae * C57BL/6)	MGI:3512273
hm2	Ep300^tm1Dli/Ep300^tm1Dli	involves: 129S4/SvJae * C57BL/6	MGI:3512284
ht3	Ep300^tm1Dli/Ep300^+	either: 129S4/SvJae or (involves: 129S4/SvJae * C57BL/6)	MGI:3512271
ht4	Ep300^tm1Dli/Ep300^+	involves: 129S4/SvJae * C57BL/6	MGI:3512285
cx5	Crebbp^tm1Dli/Crebbp^+ Ep300^tm1Dli/Ep300^+	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6	MGI:3512279

Genotype
MGI:3512273

hm1

• Allelic Composition: Ep300^tm1Dli/Ep300^tm1Dli
• Genetic Background: either: 129S4/SvJae or (involves: 129S4/SvJae * C57BL/6)

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

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:47301 )

• homozygotes appear abnormal as early as E8.5 and die between E9.0 and E11.5

• at E10.5, 50% of homozygotes show either absence of heart beating or signs of reabsorption

cardiovascular system

abnormal vitelline vasculature morphology ( J:47301 )

• at E10.5, ~20% of homozygotes display a poorly vascularized yolk sac

absent trabeculae carneae ( J:47301 )

• at E10.5, homozygotes display significantly reduced ventricular trabeculation relative to wild-type

enlarged heart ( J:47301 )

• at E10.5, ~20% of homozygotes have an enlarged heart cavity

pericardial effusion ( J:47301 )

• at E10.5, homozygotes with an enlarged heart display pericardial effusion

decreased cardiac muscle contractility ( J:47301 )

• at E10.5, the heart contractions in mutant embryos appear to be weaker and less extensive than in wild-type embryos

cellular

abnormal cell physiology ( J:47301 )

• mutant MEFs display impaired retinoic acid receptor activity; in contrast, cAMP-dependent signaling appears unaffected

decreased fibroblast proliferation ( J:47301 )

• in addition to mutant embryos, isolated MEFs show a proliferation defect, growing much slower and for fewer generations relative to wild-type

• MEFs derived from 129/Sv inbred embryos exhibit more severe proliferative defects than 129/Sv x C57BL/6 MEFs

early cellular replicative senescence ( J:47301 )

• unlike heterozygous and wild-type cells, homozygous mutant MEFs stop dividing after 3 to 4 cell generations

embryo

abnormal vitelline vasculature morphology ( J:47301 )

• at E10.5, ~20% of homozygotes display a poorly vascularized yolk sac

incomplete embryo turning ( J:47301 )

• at E10.5, the most severe but still viable homozygotes display incomplete embryo turning

embryonic growth retardation ( J:47301 )

• at E10.5, the most severe but still viable homozygotes exhibit a developmental arrest at ~E8.5-E9.0

decreased embryo size ( J:47301 )

• at E10.5, homozygotes are much smaller than wild-type embryos and appear developmentally retarded

incomplete somite formation ( J:47301 )

• at E10.5, the most severe but still viable homozygotes contain only 12-16 somites

• at this stage, mutant somites appear disorganized relative to wild-type

growth/size/body

enlarged heart ( J:47301 )

• at E10.5, ~20% of homozygotes have an enlarged heart cavity

embryonic growth retardation ( J:47301 )

• at E10.5, the most severe but still viable homozygotes exhibit a developmental arrest at ~E8.5-E9.0

decreased embryo size ( J:47301 )

• at E10.5, homozygotes are much smaller than wild-type embryos and appear developmentally retarded

muscle

absent trabeculae carneae ( J:47301 )

• at E10.5, homozygotes display significantly reduced ventricular trabeculation relative to wild-type

decreased cardiac muscle contractility ( J:47301 )

• at E10.5, the heart contractions in mutant embryos appear to be weaker and less extensive than in wild-type embryos

homeostasis/metabolism

pericardial effusion ( J:47301 )

• at E10.5, homozygotes with an enlarged heart display pericardial effusion

Genotype
MGI:3512284

hm2

• Allelic Composition: Ep300^tm1Dli/Ep300^tm1Dli
• Genetic Background: involves: 129S4/SvJae * C57BL/6

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:47301 )

• a few of 129/Sv x C57BL/6 embryos survive beyond E10.5, such mutants exhibit a less severe phenotype but die after E11.5

embryo

embryonic growth arrest ( J:47301 )

• notably, 129/Sv C57BL/6 mutant embryos tend to arrest a day or so later than 129/Sv embryos

decreased embryo size ( J:47301 )

• late-arresting 129/Sv C57BL/6 mutant embryos are smaller than wild-type embryos but show no gross patterning defects

open neural tube ( J:47301 )

• late-arresting 129/Sv C57BL/6 mutant embryos show a severe open neural tube defect

• the neural tube either fails to fuse from hindbrain to the forebrain region or remains completely open in severely affected embryos

kinked neural tube ( J:47301 )

• in homozygotes, the neural tube often shows a kinked morphology as opposed to the straight one found in wild-type

growth/size/body

abnormal facial morphology ( J:47301 )

• in homozygotes, the facial structure is collapsed

decreased embryo size ( J:47301 )

• late-arresting 129/Sv C57BL/6 mutant embryos are smaller than wild-type embryos but show no gross patterning defects

craniofacial

abnormal facial morphology ( J:47301 )

• in homozygotes, the facial structure is collapsed

vision/eye

microphthalmia ( J:47301 )

• the eyes of homozygous mutant embryos are smaller than those of wild-type embryos

nervous system

open neural tube ( J:47301 )

• late-arresting 129/Sv C57BL/6 mutant embryos show a severe open neural tube defect

• the neural tube either fails to fuse from hindbrain to the forebrain region or remains completely open in severely affected embryos

kinked neural tube ( J:47301 )

• in homozygotes, the neural tube often shows a kinked morphology as opposed to the straight one found in wild-type

exencephaly ( J:47301 )

• all 129/Sv C57BL/6 mutant embryos exhibit various degrees of exencephaly

• the neural lumen (ventricle) is collapsed; abnormal masses of neural tissue are also observed

Genotype
MGI:3512271

ht3

• Allelic Composition: Ep300^tm1Dli/Ep300⁺
• Genetic Background: either: 129S4/SvJae or (involves: 129S4/SvJae * C57BL/6)

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:47301 )

• a fraction of heterozygotes die as early as at E10.5

• at weaning, 55% fewer heterozygotes are obtained on a 129/Sv inbred genetic background

• Background Sensitivity: considerably less lethality is observed on a mixed 129 x C57BL/6 background and none on an incipient congenic C57BL/6 background

embryo

decreased embryo size ( J:47301 )

• at E10.5, heterozygotes with exencephaly are consistently smaller than wild-type embryos

open neural tube ( J:47301 )

• a fraction of heterozygotes exhibit defective neural tube closure

• in heterozygotes, the neural tube defect is restricted to the anterior part of the hindbrain and the midbrain; the rest of the neural tube fuses normally

• Background Sensitivity: considerably less lethality is observed on a mixed 129 x C57BL/6 background and none on an incipient congenic C57BL/6 background

growth/size/body

decreased embryo size ( J:47301 )

• at E10.5, heterozygotes with exencephaly are consistently smaller than wild-type embryos

nervous system

open neural tube ( J:47301 )

• a fraction of heterozygotes exhibit defective neural tube closure

• in heterozygotes, the neural tube defect is restricted to the anterior part of the hindbrain and the midbrain; the rest of the neural tube fuses normally

• Background Sensitivity: considerably less lethality is observed on a mixed 129 x C57BL/6 background and none on an incipient congenic C57BL/6 background

exencephaly ( J:47301 )

• at E10.5, 6% of 129/Sv C57BL/6 and 19% of 129/Sv heterozygous mutant embryos display exencephaly

• the neural lumen (ventricle) is collapsed; abnormal masses of neural tissue are also observed

Genotype
MGI:3512285

ht4

• Allelic Composition: Ep300^tm1Dli/Ep300⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

neoplasm

neoplasm ( J:60630 )

N • at 10-21 months, heterozygotes show no increased incidence of hematologic malignancies compared with wild-type mice

hematopoietic system

hematopoietic system phenotype ( J:60630 )

N • at 12-18 months, heterozygotes exhibit neither splenomegaly nor hematopoietic differentiation defects

Genotype
MGI:3512279

cx5

• Allelic Composition: Crebbp^tm1Dli/Crebbp⁺; Ep300^tm1Dli/Ep300⁺
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6

mortality/aging

prenatal lethality, complete penetrance ( J:47301 )

• unexpectedly, compound heterozygotes die in utero

embryo

decreased embryo size ( J:47301 )

• compound heterozygotes are smaller than control embryos

open neural tube ( J:47301 )

• compound heterozygotes exhibit a severe open neural tube defect similar to that observed in Ep300^tm1Dli or Crebbp^tm1Dli homozygous mutants

growth/size/body

decreased embryo size ( J:47301 )

• compound heterozygotes are smaller than control embryos

nervous system

open neural tube ( J:47301 )

• compound heterozygotes exhibit a severe open neural tube defect similar to that observed in Ep300^tm1Dli or Crebbp^tm1Dli homozygous mutants

exencephaly ( J:47301 )

• compound heterozygotes exhibit extensive exencephaly