Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse   Donating Investigator David Livingston,   Dana-Farber Cancer Institute

Description
Mice that are homozygous null for the Ep300 gene are embryonic lethal, dying between embryonic days 9 and 11.5 exhibiting defects in neurulation, cell proliferation and heart development. Isolated embryonic fibroblasts display a proliferation defect, growing much slower and for fewer generations than embryonic fibroblasts derived from wild type embryos. Mice heterozygous for the null allele also exhibit a degree of embryonic lethality, a trait apparently influenced by genetic background. The highest lethality in heterozygotes is observed on a 129 background, with considerably less seen on a mixed B6;129 background and none on an incipient congenic C57BL/6 background.

Development
A targeting vector containing a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter was used to disrupt three exons encoding the first Cys/His domain of the Ep300 gene. A herpes simplex virus thymidine kinase was used for negative selection. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were backcrossed to C57BL/6 mice.

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Ep300^tm1Dli/Ep300⁺

        either: 129S4/SvJae or (involves: 129S4/SvJae * C57BL/6)

• mortality/aging
• partial embryonic lethality during organogenesis
  • a fraction of heterozygotes die as early as at E10.5   (MGI Ref ID J:47301)
  • at weaning, 55% fewer heterozygotes are obtained on a 129/Sv inbred genetic background   (MGI Ref ID J:47301)
  • considerably less lethality is observed on a mixed 129 x C57BL/6 background and none on an incipient congenic C57BL/6 background   (MGI Ref ID J:47301)
• embryogenesis phenotype
• decreased embryo size
  • at E10.5, heterozygotes with exencephaly are consistently smaller than wild-type embryos   (MGI Ref ID J:47301)
• open neural tube
  • a fraction of heterozygotes exhibit defective neural tube closure   (MGI Ref ID J:47301)
  • 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   (MGI Ref ID J:47301)
  • considerably less lethality is observed on a mixed 129 x C57BL/6 background and none on an incipient congenic C57BL/6 background   (MGI Ref ID J:47301)
• growth/size phenotype
• decreased embryo size
  • at E10.5, heterozygotes with exencephaly are consistently smaller than wild-type embryos   (MGI Ref ID J:47301)
• nervous system phenotype
• exencephaly
  • at E10.5, 6% of 129/Sv × C57BL/6 and 19% of 129/Sv heterozygous mutant embryos display exencephaly   (MGI Ref ID J:47301)
  • the neural lumen (ventricle) is collapsed; abnormal masses of neural tissue are also observed   (MGI Ref ID J:47301)
• open neural tube
  • a fraction of heterozygotes exhibit defective neural tube closure   (MGI Ref ID J:47301)
  • 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   (MGI Ref ID J:47301)
  • considerably less lethality is observed on a mixed 129 x C57BL/6 background and none on an incipient congenic C57BL/6 background   (MGI Ref ID J:47301)

Ep300^tm1Dli/Ep300⁺

        involves: 129S4/SvJae * C57BL/6

• tumorigenesis
• *normal* tumorigenesis
  • at 10-21 months, heterozygotes show no increased incidence of hematologic malignancies compared with wild-type mice   (MGI Ref ID J:60630)
• hematopoietic system phenotype
• *normal* hematopoietic system phenotype
  • at 12-18 months, heterozygotes exhibit neither splenomegaly nor hematopoietic differentiation defects   (MGI Ref ID J:60630)

Ep300^tm1Dli/Ep300^tm1Dli

        either: 129S4/SvJae or (involves: 129S4/SvJae * C57BL/6)

• mortality/aging
• partial embryonic lethality during organogenesis
  • homozygotes appear abnormal as early as E8.5 and die between E9.0 and E11.5   (MGI Ref ID J:47301)
  • at E10.5, 50% of homozygotes show either absence of heart beating or signs of reabsorption   (MGI Ref ID J:47301)
• cardiovascular system phenotype
• abnormal vitelline vasculature morphology
  • at E10.5, ~20% of homozygotes display a poorly vascularized yolk sac   (MGI Ref ID J:47301)
• absent trabeculae carneae
  • at E10.5, homozygotes display significantly reduced ventricular trabeculation relative to wild-type   (MGI Ref ID J:47301)
• decreased cardiac muscle contractility
  • at E10.5, the heart contractions in mutant embryos appear to be weaker and less extensive than in wild-type embryos   (MGI Ref ID J:47301)
• enlarged heart
  • at E10.5, ~20% of homozygotes have an enlarged heart cavity   (MGI Ref ID J:47301)
• pericardial effusion
  • at E10.5, homozygotes with an enlarged heart display pericardial effusion   (MGI Ref ID J:47301)
• cellular phenotype
• abnormal cell physiology
  • mutant MEFs display impaired retinoic acid receptor activity; in contrast, cAMP-dependent signaling appears unaffected   (MGI Ref ID J:47301)
• • decreased cell proliferation
    • in addition to mutant embryos, isolated MEFs show a proliferation defect, growing much slower and for fewer generations relative to wild-type   (MGI Ref ID J:47301)
    • unlike heterozygous and wild-type cells, homozygous mutant MEFs stop dividing after 3 to 4 cell generations   (MGI Ref ID J:47301)
    • MEFs derived from 129/Sv inbred embryos exhibit more severe proliferative defects than 129/Sv x C57BL/6 MEFs   (MGI Ref ID J:47301)
• embryogenesis phenotype
• abnormal vitelline vasculature morphology
  • at E10.5, ~20% of homozygotes display a poorly vascularized yolk sac   (MGI Ref ID J:47301)
• decreased embryo size
  • at E10.5, homozygotes are much smaller than wild-type embryos and appear developmentally retarded   (MGI Ref ID J:47301)
• embryonic growth retardation
  • at E10.5, the most severe but still viable homozygotes exhibit a developmental arrest at ~E8.5-E9.0   (MGI Ref ID J:47301)
• incomplete embryo turning
  • at E10.5, the most severe but still viable homozygotes display incomplete embryo turning   (MGI Ref ID J:47301)
• incomplete somite formation
  • at E10.5, the most severe but still viable homozygotes contain only 12-16 somites   (MGI Ref ID J:47301)
  • at this stage, mutant somites appear disorganized relative to wild-type   (MGI Ref ID J:47301)
• growth/size phenotype
• decreased embryo size
  • at E10.5, homozygotes are much smaller than wild-type embryos and appear developmentally retarded   (MGI Ref ID J:47301)
• embryonic growth retardation
  • at E10.5, the most severe but still viable homozygotes exhibit a developmental arrest at ~E8.5-E9.0   (MGI Ref ID J:47301)
• muscle phenotype
• absent trabeculae carneae
  • at E10.5, homozygotes display significantly reduced ventricular trabeculation relative to wild-type   (MGI Ref ID J:47301)
• decreased cardiac muscle contractility
  • at E10.5, the heart contractions in mutant embryos appear to be weaker and less extensive than in wild-type embryos   (MGI Ref ID J:47301)
• homeostasis/metabolism phenotype
• pericardial effusion
  • at E10.5, homozygotes with an enlarged heart display pericardial effusion   (MGI Ref ID J:47301)

Ep300^tm1Dli/Ep300^tm1Dli

        involves: 129S4/SvJae * C57BL/6

• mortality/aging
• complete embryonic lethality during organogenesis
  • 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   (MGI Ref ID J:47301)
• craniofacial phenotype
• abnormal head morphology
  • in homozygotes, the facial structure is collapsed   (MGI Ref ID J:47301)
• embryogenesis phenotype
• decreased embryo size
  • late-arresting 129/Sv × C57BL/6 mutant embryos are smaller than wild-type embryos but show no gross patterning defects   (MGI Ref ID J:47301)
• embryonic growth arrest
  • notably, 129/Sv × C57BL/6 mutant embryos tend to arrest a day or so later than 129/Sv embryos   (MGI Ref ID J:47301)
• kinked neural tube
  • in homozygotes, the neural tube often shows a kinked morphology as opposed to the straight one found in wild-type   (MGI Ref ID J:47301)
• open neural tube
  • late-arresting 129/Sv × C57BL/6 mutant embryos show a severe open neural tube defect   (MGI Ref ID J:47301)
  • the neural tube either fails to fuse from hindbrain to the forebrain region or remains completely open in severely affected embryos   (MGI Ref ID J:47301)
• growth/size phenotype
• decreased embryo size
  • late-arresting 129/Sv × C57BL/6 mutant embryos are smaller than wild-type embryos but show no gross patterning defects   (MGI Ref ID J:47301)
• vision/eye phenotype
• microphthalmia
  • the eyes of homozygous mutant embryos are smaller than those of wild-type embryos   (MGI Ref ID J:47301)
• nervous system phenotype
• exencephaly
  • all 129/Sv × C57BL/6 mutant embryos exhibit various degrees of exencephaly   (MGI Ref ID J:47301)
  • the neural lumen (ventricle) is collapsed; abnormal masses of neural tissue are also observed   (MGI Ref ID J:47301)
• kinked neural tube
  • in homozygotes, the neural tube often shows a kinked morphology as opposed to the straight one found in wild-type   (MGI Ref ID J:47301)
• open neural tube
  • late-arresting 129/Sv × C57BL/6 mutant embryos show a severe open neural tube defect   (MGI Ref ID J:47301)
  • the neural tube either fails to fuse from hindbrain to the forebrain region or remains completely open in severely affected embryos   (MGI Ref ID J:47301)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Ep300^tm1Dli related

Developmental Biology Research
Embryonic Lethality (Homozygous)

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Ep300tm1Dli
Allele Name		targeted mutation 1, David Livingston
Allele Type		Targeted (knock-out)
Common Name(s)		p300-;
Mutation Made By		Andrew Kung,   Dana-Farber Cancer Institute
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Ep300, E1A binding protein p300
Chromosome		15
Gene Common Name(s)		KAT3B; RSTS2; p300;
Molecular Note		A genomic fragment containing exons encoding the first cys/his rich domain were replaced with a neomycin selection cassette. Western blot analysis on embryonic fibroblasts derived from homozygous E10.5 embryos demonstrated that no detectable protein wasexpressed. [MGI Ref ID J:47301]

Genotyping

Genotyping Information

Genotyping Protocols

Ep300 ^tm1Dli, Separated PCR
NEOTD (Generic Neo), Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Yao TP; Oh SP; Fuchs M; Zhou ND; Ch'ng LE; Newsome D; Bronson RT ; Li E ; Livingston DM ; Eckner R. 1998. Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell 93(3):361-72. [PubMed: 9590171]  [MGI Ref ID J:47301]

Additional References

Ep300^tm1Dli related

Braganca J; Eloranta JJ; Bamforth SD; Ibbitt JC; Hurst HC; Bhattacharya S. 2003. Physical and functional interactions among AP-2 transcription factors, p300/CREB-binding protein, and CITED2. J Biol Chem 278(18):16021-9. [PubMed: 12586840]  [MGI Ref ID J:156240]

Kung AL; Rebel VI; Bronson RT; Ch'ng LE; Sieff CA; Livingston DM; Yao TP. 2000. Gene dose-dependent control of hematopoiesis and hematologic tumor suppression by CBP. Genes Dev 14(3):272-7. [PubMed: 10673499]  [MGI Ref ID J:60630]

Lopez-Atalaya JP; Ciccarelli A; Viosca J; Valor LM; Jimenez-Minchan M; Canals S; Giustetto M; Barco A. 2011. CBP is required for environmental enrichment-induced neurogenesis and cognitive enhancement. EMBO J 30(20):4287-98. [PubMed: 21847097]  [MGI Ref ID J:177196]

Phan HM; Xu AW; Coco C; Srajer G; Wyszomierski S; Evrard YA; Eckner R; Dent SY. 2005. GCN5 and p300 share essential functions during early embryogenesis. Dev Dyn 233(4):1337-47. [PubMed: 15937931]  [MGI Ref ID J:99573]

Viosca J; Lopez-Atalaya JP; Olivares R; Eckner R; Barco A. 2010. Syndromic features and mild cognitive impairment in mice with genetic reduction on p300 activity: Differential contribution of p300 and CBP to Rubinstein-Taybi syndrome etiology. Neurobiol Dis 37(1):186-94. [PubMed: 19822209]  [MGI Ref ID J:156907]

Xu CR; Cole PA; Meyers DJ; Kormish J; Dent S; Zaret KS. 2011. Chromatin 'prepattern' and histone modifiers in a fate choice for liver and pancreas. Science 332(6032):963-6. [PubMed: 21596989]  [MGI Ref ID J:172635]

Zimmer SN; Zhou Q; Zhou T; Cheng Z; Abboud-Werner SL; Horn D; Lecocke M; White R; Krivtsov AV; Armstrong SA; Kung AL; Livingston DM; Rebel VI. 2011. Crebbp haploinsufficiency in mice alters the bone marrow microenvironment, leading to loss of stem cells and excessive myelopoiesis. Blood 118(1):69-79. [PubMed: 21555743]  [MGI Ref ID J:174893]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Colony Maintenance

Breeding & Husbandry	This strain originated on a B6;129 background and has been backcrossed to C57BL/6 for at least 6 generations(5/2001).

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• This strain is included in the Induced Mutant Resource Colony collection.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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