Description

Strain Information

Type Mutant Stock; Targeted Mutation; Species laboratory mouse   Donating Investigator Celeste Simon,   University of Pennsylvania

Description
These mice possess loxP sites on either side of exon 2 of the targeted gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon deleted in the cre-expressing tissue(s).

For example, when bred to a strain with inducible Cre recombinase expression in cardiac cells (see Stock No. 005657 for example), this mutant mouse strain may be useful in studies of erythropoiesis.

When bred to a strain with tamoxifen inducible widespread Cre recombinase expression(see Stock No. 008085 for example), this mutant mouse strain may be useful in studies of erythropoiesis.

Development
A loxP site flanked targeting vector containing PGK-Neo selection cassette was utilized in the construction of this mutant. This selection cassette was inserted downstream of exon 2 of the targeted gene, and another loxP site was inserted upstream of exon 2. This construct was electroporated into 129X1/SvJ derived RW-4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to transgenic mice (on the C57BL/6 genetic background) expressing Cre recombinase under the control of the adenovirus EIIa promoter. Mice that retained the loxP site flanked exon 2 were then bred to C57BL/6 mice to remove the EIIa-cre transgene. Heterozygotes were crossed to generate homozygotes.

Related Strains

Strains carrying other alleles of Epas1

003266

B6;129S7-Epas1tm1Rus/J

View Strains carrying other alleles of Epas1     (1 strain)

Additional Web Information

Cre-lox Systems

Phenotype

Phenotype Information

Mammalian Phenotype Terms assigned by genotype

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

Epas1^tm1Mcs/Epas1^tm1.1Mcs Tg(UBC-cre/ESR1)1Ejb/0

        involves: 129X1/SvJ * FVB/N   (conditional)

• hematopoietic system phenotype
• abnormal hematopoietic system physiology (MGI Ref ID J:119731)
  • mice show weak induction of erythropoietin after phenylhydrazine treatment
• abnormal proerythroblast morphology (MGI Ref ID J:119731)
  • erythroid progenitors from bone marrow form ~50% fewer erythroid burst-forming units (BFU-E) and colony-forming units (CFU-E) in culture than control cells, whereas erythroid progenitors from the spleen form more BFU-E and CFU-E
  • there are fewer CD71+ immature erythroid progenitors in the bone marrow, and a higher percentage of CD71+ /Ter119+ double positive cells in the spleen
• abnormal reticulocyte morphology (MGI Ref ID J:119731)
  • numbers are decreased compared to controls
• anemia (MGI Ref ID J:119731)
  • occurs after postnatal cre induction
• decreased erythrocyte cell number (MGI Ref ID J:119731)
  • with acute deletion of Epas1 at 6-8 weeks induced by tamoxifen administration, animals have decreased red blood cell numbers relative to controls
• decreased hematocrit (MGI Ref ID J:119731)
  • with acute deletion of Epas1 at 6-8 weeks induced by tamoxifen administration, animals have decreased hematocrit relative to controls
• decreased hemoglobin content (MGI Ref ID J:119731)
  • with acute deletion of Epas1 at 6-8 weeks induced by tamoxifen administration, animals have decreased hemoglobin levels relative to controls
• enlarged spleen (MGI Ref ID J:119731)
  • spleens are enlarged relative to controls (0.5% spleen weight to body weight vs. ~0.4% in controls)
• immune system phenotype
• enlarged spleen (MGI Ref ID J:119731)
  • spleens are enlarged relative to controls (0.5% spleen weight to body weight vs. ~0.4% in controls)

Research Applications

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

Neurobiology Research
Cre-lox System (loxP-flanked Sequences)

Research Tools
Cardiovascular Research (Cre-lox System)
Cre-lox System (loxP-flanked Sequences)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Epas1tm1Mcs
Allele Name		targeted mutation 1, M Celeste Simon
Common Name(s)		Epas12lox; Hif-2alpha 2-lox;
Mutation Made By		Celeste Simon,   University of Pennsylvania
Strain of Origin		129X1/SvJ
ES Cell Line Name		RW-4
ES Cell Line Strain		129X1/SvJ
Gene Symbol and Name		Epas1, endothelial PAS domain protein 1
Chromosome		17
Gene Common Name(s)		ECYT4; HIF-2alpha; HIF1 alpha-like factor; HIF2A; HLF; HRF; Hif like protein; MOP2; PASD2; hypoxia inducible transcription factor 2alpha;
Molecular Note		Exon 2 was flanked with loxP sites. [MGI Ref ID J:119731]

Genotyping

Genotyping Information

Genotyping Protocols

Epas1^tm1Mcs, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Gruber M; Hu CJ; Johnson RS; Brown EJ; Keith B; Simon MC. 2007. Acute postnatal ablation of Hif-2alpha results in anemia. Proc Natl Acad Sci U S A 104(7):2301-6. [PubMed: 17284606]  [MGI Ref ID J:119731]

Additional References

Epas1^tm1Mcs related

Rankin EB; Biju MP; Liu Q; Unger TL; Rha J; Johnson RS; Simon MC; Keith B; Haase VH. 2007. Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo. J Clin Invest 117(4):1068-77. [PubMed: 17404621]  [MGI Ref ID J:121253]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

 

This strain is currently Under Development for Distribution Colony.
To register your interest in this strain go to the Strain Interest Form.

Estimated Available for Sale Date:

Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.

View All Strains Under Development

General Terms and Conditions

View JAX^® Mice & Services Conditions of Use.

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

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.

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