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| These mutant mice carrying a (floxed) Epas1 (endothelial PAS domain protein 1) allele, Epas12lox, may be useful in generating conditional mutations for studies related to erythropoiesis. | |||||||||||
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.
Strains carrying other alleles of Epas1
003266 B6;129S7-Epas1tm1Rus/J View Strains carrying other alleles of Epas1 (1 strain)
Cre-lox Systems
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.Epas1tm1Mcs/Epas1tm1.1Mcs 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)
| 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 Protocols
Epas1tm1Mcs, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
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]
Epas1tm1Mcs 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]
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice can be bred as homozygotes.
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
Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.
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