Description

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. Mating System Heterozygote x Heterozygote         (Female x Male)   22-FEB-13 Species laboratory mouse Generation N9pN1+F1 (14-MAY-13) Generation Definitions   Donating Investigator Robert G Oshima,   Sanford-Burnham Medical Research Institute

Description
Homozygous Ets2^flox mice are viable and fertile. The Ets2^flox allele has loxP sites flanking exons 9-10 of the E26 avian leukemia oncogene 2 (Ets2) gene. When bred to mice that express Cre recombinase, the resulting offspring will have the sequences encoding the C-terminal portion of the Ets2 DNA-binding domain deleted in the cre-expressing tissues. This is designed to result in an inactive Ets2 protein lacking a functional DNA-binding domain (the deleted allele is called Ets2^db2).

When Ets2^flox mice are bred to mice with Cre recombinase expression in embryonic/germ cells (MORE-Cre; Stock No. 003755), the resulting homozygous mice with pan deletion of the Ets2 DNA binding domain exhibit embryonic lethality similar to Ets2 knockout mice. Furthermore, such mice may be used to study mammary epithelial tumor microenvironment when bred to also harbor transgenes expressing either Polyoma virus middle T antigen (see MMTV-PyVT mice [Stock No. 002374]) or activated Neu/ErbB2 (see MMTV-Neu/ErbB2 mice [Stock No. 005038]).

In addition, when Ets2^flox mice are bred to a strain expressing Cre recombinase in intestinal epithelial tissues (Villin-Cre; Stock No. 004586), the resulting mice are useful in studying intestinal stem cells, colon crypt development, and chemical carcinogen-induced colon tumorigenesis.

Development
A targeting vector was designed to insert an frt-flanked PGK-neo cassette and a loxP site upstream of exon 9, and a second loxP site downstream of exon 10 of the E26 avian leukemia oncogene 2 (Ets2) gene. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric mice were bred with FVB/NJ mice to establish the Ets2^flox-neo colony. To remove the frt-flanked PGK-neo cassette, embryos from Ets2^flox-neo mice were isolated and then microinjected with a pCAGGS-Flpe plasmid. The resulting floxed exons 9-10 allele (a single frt site and first loxP site remaining upstream of exon 9, and a second loxP site downstream of exon 10) is called Ets2^flox. These Ets2^flox mice were subsequently backcrossed to FVB/NJ mice for at least nine generations prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred to FVB/NJ inbred mice (Stock No. 001800) for at least one generation to establish The Jackson Laboratory Repository colony.

Control Information

	Control
	001800 FVB/NJ
Considerations for Choosing Controls

Additional Web Information

Introduction to Cre-lox technology

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.

Ets2^tm3Rgo/Ets2^tm3Rgo

        involves: 129S1/Sv * 129X1/SvJ

• normal phenotype
• no abnormal phenotype detected
  • mice have normal development and lifespan   (MGI Ref ID J:128952)

Ets2^tm3Rgo/Ets2^tm3Rgo

        involves: 129S1/Sv * 129X1/SvJ   (conditional)

• embryogenesis phenotype
• abnormal trophoblast layer morphology
  • when transfected with an adenovirus Cre, trophoblast stem cells exhibit reduced growth and self-renewal   (MGI Ref ID J:128952)
  • however, trophoblast cells transfected with an adenovirus Cre differentiate normally   (MGI Ref ID J:128952)

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Ets2^tm3Rgo/Ets2^tm3Rgo Meox2^tm1(cre)Sor/Meox2⁺

        involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ   (conditional)

• mortality/aging
• complete embryonic lethality between somite formation and embryo turning
  • mice die around E8   (MGI Ref ID J:128952)
• embryogenesis phenotype
• abnormal visceral yolk sac morphology
  • at E7.5, yolk sacs are cone-shaped   (MGI Ref ID J:128952)
• decreased embryo size
  • at E7.5   (MGI Ref ID J:128952)
• growth/size phenotype
• decreased embryo size
  • at E7.5   (MGI Ref ID J:128952)

View Research Applications

Research Applications

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

Cancer Research
Genes Regulating Growth and Proliferation
Growth Factors/Receptors/Cytokines
Oncogenes
Other
Tumor Resistance
Tumor Suppressor Genes

Cell Biology Research
Signal Transduction
Transcriptional Regulation

Immunology, Inflammation and Autoimmunity Research
Intracellular Signaling Molecules

Research Tools
Cancer Research
      anti-tumor activity
Cre-lox System
      loxP-flanked Sequences
Genetics Research
      Mutagenesis and Transgenesis: Cre-lox System
      Mutagenesis and Transgenesis: transcriptional activation

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Ets2tm3Rgo
Allele Name		targeted mutation 3, Robert G Oshima
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Ets2flox; Ets2tm4Rgo;
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Ets2, E26 avian leukemia oncogene 2, 3' domain
Chromosome		16
Gene Common Name(s)		AU022856; ETS2IT1; Ets-2; expressed sequence AU022856;
Molecular Note		An frt-flanked neo cassette with a 3' loxP site was inserted into intron 8 and an additional loxP site was inserted into the 3' UTR. The neo cassette was removed by flp-mediated recombination using a transiently expressing vector. [MGI Ref ID J:128952]

Genotyping

Genotyping Information

Genotyping Protocols

Ets2^tm3Rgo, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Munera J; Cecena G; Jedlicka P; Wankell M; Oshima RG. 2011. Ets2 regulates colonic stem cells and sensitivity to tumorigenesis. Stem Cells 29(3):430-9. [PubMed: 21425406]  [MGI Ref ID J:171112]

Tynan JA; Wen F; Muller WJ; Oshima RG. 2005. Ets2-dependent microenvironmental support of mouse mammary tumors. Oncogene 24(46):6870-6. [PubMed: 16007139]  [MGI Ref ID J:102368]

Wen F; Tynan JA; Cecena G; Williams R; Munera J; Mavrothalassitis G; Oshima RG. 2007. Ets2 is required for trophoblast stem cell self-renewal. Dev Biol 312(1):284-99. [PubMed: 17977525]  [MGI Ref ID J:128952]

Additional References

Ets2^tm3Rgo related

Morioka Y; Isotani A; Oshima RG; Okabe M; Ikawa M. 2009. Placenta-specific gene activation and inactivation using integrase-defective lentiviral vectors with the Cre/LoxP system. Genesis 47(12):793-8. [PubMed: 19830817]  [MGI Ref ID J:156029]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together.
Mating System	Heterozygote x Heterozygote         (Female x Male)   22-FEB-13
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	001800 FVB/NJ
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

The Jackson Laboratory's Genotype Promise

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.

---

Ordering Information
JAX^® Mice
Surgical and Preconditioning Services
JAX^® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Notice to customers in Canada.
- Use of MICE by companies or for-profit entities requires a license.

Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.