Overview

Also Known As:Ezh2^fl

These Ezh2^F/F mutant mice possess loxP sites flanking exons 14-15 of the zeste homolog 2 (Ezh2) gene. This strain may be useful for studying chromatin condensation and gene silencing.

Donating Investigator

Stuart H Orkin, Harvard University

Genetic overview

Genetic Background	Generation
	?+pN1F18 (2020-01-20 00:00:00)

Ezh2^tm2Sho

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Ezh2	enhancer of zeste 2 polycomb repressive complex 2 subunit

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Research Applications

Research Tools
Cell Biology Research

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Base Price

Starting at:

$255.00 Domestic price for female 4-week

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Details

Detailed Description

These Ezh2^F/F mice possess loxP sites flanking exons 14-15 of the zeste homolog 2 (Ezh2) gene. EZH2 is part of polycomb repressive complexes (PRC) 2. PRC2 is involved in transcriptional repression by the addition of three methyl groups to histone 3 during chromatin condensation. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 14-15 deleted in cre-expressing tissues.

For example, when crossed to B6.Cg-Tg(Mx1-cre)1Cgn/J mice (Stock No. 003556) expressing Cre recombinase after poly I:C treatment, Ezh2 deficiency leads to the development of spontaneous T-cell leukemia (T-ALL) 122-281 days following treatment.

Development

A targeting vector was designed to insert a loxP-flanked neomycin resistance (neo) cassette upstream of exon 14, and a single loxP site downstream of exon 15 of the enhancer of zeste homolog 2 (Ezh2) gene. The construct was electroporated into 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺-derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a Cre expression plasmid to delete the neo cassette. Resulting ES cells contained multiple gene rearrangments; intact floxed-exons 14-15, intact floxed-neo cassette, or excision of both exons and the neo cassette. Correctly targeted ES cells, containing only the floxed-exons 14-15, were injected into blastocysts and resulting chimeric mice were maintained on a mixed background. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Control Suggestions

None Available

Additional Information

Considerations for Choosing Controls

Selected References

Shen X; Liu Y; Hsu YJ; Fujiwara Y; Kim J; Mao X; Yuan GC; Orkin SH. 2008. EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency. Mol Cell 32(4):491-502PubMed: 19026780 MGI: J:142193

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Genetics

Ezh2^tm2Sho

Allele Symbol: Ezh2^tm2Sho

Allele Name	targeted mutation 2, Stuart Orkin
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	Ezh2^fl
Gene Symbol and Name	Ezh2, enhancer of zeste 2 polycomb repressive complex 2 subunit
Gene Synonym(s)
Strain of Origin	129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Chromosome	6
Molecular Note	A floxed neo cassette was inserted into intron 13 and an additional loxP site was inserted into intron 15. Transient cre expression was used to remove the neo cassette in ES cells leaving exons 14 and 15 floxed.

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

acute lymphoblastic leukemia

Research Areas By Phenotype

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

Research Tools
- Cre-lox System
  - loxP-flanked Sequences
Cell Biology Research
- Cell Cycle Regulation
- Transcriptional Regulation

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Ezh2^tm2Sho/Ezh2^tm2Sho Tg(Mx1-cre)1Cgn/0
involves: 129S1/Sv * C57BL/6 * CBA

endocrine/exocrine gland phenotype

decreased thymocyte number
- 7-8 week old mice treated with pIpC to induce cre expression exhibit a 7-10-fold decrease in the numbers of thymocytes

neoplasm

increased leukemia incidence
- leukemias are phenotypically heterogenous
- leukemic cells infiltrate the bone marrow, spleen, liver, and kidney infiltrates comprise a mixture of mature lymphoid cells with open chromatin and cells with blastic appearance and prominent nucleoli
- mice treated with pIpC to induce cre expression develop spontaneous T-cell leukemia (T-ALL), with a latency of development of 122-281 days following pIpC treatment

growth/size/body region phenotype

enlarged spleen
- mice treated with pIpC to induce cre expression exhibit an enlarged spleen

hematopoietic system phenotype

decreased double-positive T cell number
- 7-8 week old mice treated with pIpC to induce cre expression exhibit a decrease in CD4+CD8+ cells

decreased thymocyte number
- 7-8 week old mice treated with pIpC to induce cre expression exhibit a 7-10-fold decrease in the numbers of thymocytes

enlarged spleen
- mice treated with pIpC to induce cre expression exhibit an enlarged spleen

increased double-negative T cell number
- 7-8 week old mice treated with pIpC to induce cre expression exhibit an accumulation of immature CD4-CD8- cell population

immune system phenotype

decreased double-positive T cell number
- 7-8 week old mice treated with pIpC to induce cre expression exhibit a decrease in CD4+CD8+ cells

decreased thymocyte number
- 7-8 week old mice treated with pIpC to induce cre expression exhibit a 7-10-fold decrease in the numbers of thymocytes

enlarged lymph nodes
- mice treated with pIpC to induce cre expression exhibit enlarged lymph nodes

enlarged spleen
- mice treated with pIpC to induce cre expression exhibit an enlarged spleen

increased double-negative T cell number
- 7-8 week old mice treated with pIpC to induce cre expression exhibit an accumulation of immature CD4-CD8- cell population

Genotype: Ezh2^tm2Sho/Ezh2^tm2Sho Olig1^tm1(cre)Rth/0
involves: 129S1/Sv * 129S4/SvJae

nervous system phenotype

abnormal oligodendrocyte morphology
- lower number of Mbp+ mature oligodendrocytes in brain at age P7
- lower percentage of CC1+ differentiating oligodendrocytes amongst Olig2+ oligodendrocytes in brain at age P7

dysmyelination
- reduced myelination of axons in optic nerves at age P15
- thinner myelin sheaths around axons in optic nerves at age P15

References

Shen X; Liu Y; Hsu YJ; Fujiwara Y; Kim J; Mao X; Yuan GC; Orkin SH. 2008. EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency. Mol Cell 32(4):491-502PubMed: 19026780 MGI: J:142193

Additional - Ezh2^tm2Sho related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Ezh2
- Standard PCR:Ezh2
- Genotyping resources and troubleshooting
Dietary Information
- New Diet as of March 2015: Lab Diet® 5K0Q (6% fat)
Breeding Considerations

When maintaining a live colony mice homozygous for the floxed allele may be bred together.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Citation
When using the Ezh2^fl mouse strain in a publication, please cite the originating article(s) and include JAX stock #022616 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX10 (Standard)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Ezh2<tm2Sho>

Related Products and Services

Frozen Mouse Embryo	B6;129S1-Ezh2<tm2Sho>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6;129S1-Ezh2<tm2Sho>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6;129S1-Ezh2<tm2Sho>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6;129S1-Ezh2<tm2Sho>/J Frozen Embryo	$3373.50

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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General Terms and Conditions

Questions about Terms of Use

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Licensing Information

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Also Known As:Ezh2fl

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Ezh2tm2Sho

Allele Symbol: Ezh2tm2Sho

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Ezh2tm2Sho/Ezh2tm2Sho Tg(Mx1-cre)1Cgn/0involves: 129S1/Sv * C57BL/6 * CBA

endocrine/exocrine gland phenotype

neoplasm

growth/size/body region phenotype

hematopoietic system phenotype

immune system phenotype

Genotype: Ezh2tm2Sho/Ezh2tm2Sho Olig1tm1(cre)Rth/0involves: 129S1/Sv * 129S4/SvJae

nervous system phenotype

References

Additional - Ezh2tm2Sho related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As:Ezh2^fl

Ezh2^tm2Sho

Allele Symbol: Ezh2^tm2Sho

Genotype: Ezh2^tm2Sho/Ezh2^tm2Sho Tg(Mx1-cre)1Cgn/0
involves: 129S1/Sv * C57BL/6 * CBA

Genotype: Ezh2^tm2Sho/Ezh2^tm2Sho Olig1^tm1(cre)Rth/0
involves: 129S1/Sv * 129S4/SvJae

Additional - Ezh2^tm2Sho related