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Strain Name:
C57BL/6-Epas1tm1.1Fsl/Mmjax
Stock Number:
075769-JAX
Citation ID:
RRID:MMRRC_075769-JAX
Other Names:
Hif2a G536W

Strain Information

Epas1tm1.1Fsl
Name: endothelial PAS domain protein 1; targeted mutation 1.1, Frank Lee
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 17
Alteration at locus: Knock-In
Epas1
Name: endothelial PAS domain protein 1
Synonyms: MOP2, HIF-2alpha, Hif like protein, hypoxia inducible transcription factor 2alpha, HLF, HRF, HIF2A, bHLHe73
Type: Gene
Species: Mouse
Chromosome: 17
Alteration at locus: Knock-In
NCBI: 13819
VEGA: 17
HGNC: HGNC:3374
Homologene: 1095
Genetic Alterations
Hif2aG536W knock-in (KI) mice express a mutant exon 12 of the Epas1 gene, carrying a G536W amino acid substitution. These mice may be useful when studying erythropoiesis and the hypoxia-inducible factor (HIF) pathway.
ES Cell Line
Taconic Artemis derived from C57BL/6NTac
Phenotype
The endothelial PAS domain protein 1 (Epas1) gene encodes a subunit of the hypoxia-inducible factor (HIF) complex, referred to as hypoxia-inducible factor 2-alpha (HIF-2α). HIF is a transcription factor that regulates oxygen homeostasis by regulating pulmonary vascular tone, erythropoiesis (red blood cell production), and angiogenesis. These Hif2aG536W knock-in (KI) mice have nucleotide substitutions (GGC>TGG) in exon 12 of the Epas1 gene, resulting in a glycine to tryptophan substitution at residue 536 (G536W).

Heterozygous mice are viable and fertile. Heterozygotes and homozygotes display erythrocytosis, in a dose-dependent manner, compared to wildtype controls. The donating laboratory notes that homozygous mice are not fertile and are generated in a lower than expected Mendelian ratio from heterozygous x heterozygous matings (~13%). These mice may be useful for studying erythropoiesis, pulmonary hypertension, oxygen sensing, and the HIF pathway.

MeSH Terms
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors/genetics
  • Basic Helix-Loop-Helix Transcription Factors/metabolism
  • Blood Gas Analysis
  • Cells, Cultured
  • Disease Models, Animal
  • Endothelin-1/genetics
  • Endothelin-1/metabolism
  • Erythropoiesis
  • Erythropoietin/blood
  • Erythropoietin/genetics
  • Gene Expression
  • Gene Knock-In Techniques
  • Genetic Association Studies
  • Humans
  • Hypertension, Pulmonary/blood
  • Hypertension, Pulmonary/genetics
  • Hypertension, Pulmonary/physiopathology
  • Hypertrophy, Right Ventricular/blood
  • Hypertrophy, Right Ventricular/genetics
  • Hypertrophy, Right Ventricular/physiopathology
  • Kidney/metabolism
  • Lung/metabolism
  • Lung/pathology
  • Lung/physiopathology
  • Mice
  • Mice, Inbred C57BL
  • Mutagenesis
  • Mutation, Missense
  • Polycythemia/blood
  • Polycythemia/genetics
  • Polycythemia/physiopathology
  • Proto-Oncogene Proteins c-sis/genetics
  • Proto-Oncogene Proteins c-sis/metabolism
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Respiratory Rate
  • Up-Regulation
  • Vascular Endothelial Growth Factor A/blood
Strain GQC Summary
Gene Specific Genotyping:

To request gene-specific and other genotyping services for a strain, please contact the distribution MMRRC Center for more information.

Background Genetic Quality:

The MMRRC has developed a Genetic Quality Control pipeline using the MiniMUGA array to provide additional information to identify and validate genetic backgrounds of MMRRC strains. For more information on whether genetic background data is available, please contact MMRRC_GeneticQC@med.unc.edu. Note: that MiniMUGA genetic background data is not available on all strains, but can be ordered if desired.

Suggested Control Mice
Littermates of all relevant genotypes.
  • Hematology
  • Internal/Organ
  • Research Tools
Donor
Frank Lee, M.D., Perelman School of Medicine, University of Pennsylvania.
Primary Reference

Tan Q, Kerestes H, Percy MJ, Pietrofesa R, Chen L, Khurana TS, Christofidou-Solomidou M, Lappin TR, Lee FS. Erythrocytosis and pulmonary hypertension in a mouse model of human HIF2A gain of function mutation. J Biol Chem. 2013 Jun 14;288(24):17134-44. doi: 10.1074/jbc.M112.444059. Epub 2013 May 2. (Medline PMID: 23640890)

Strain Development

The Hif2aG536W targeting vector was designed to replace the endogenous exon 12 of the endothelial PAS domain protein 1 (Epas1) gene, with a mutant exon 12 sequence harboring nucleotide mutations (GGC>TGG) that results in a glycine to tryptophan amino acid substitution at position 536 (G536W). The targeting construct also consisted of a loxP-flanked neomycin selection cassette in intron 12. The construct was electroporated into C57BL/6-derived embryonic stem (ES) cells and correctly targeted ES cells were injected into C57BL/6 blastocysts. Chimeric mice were bred to C57BL/6 mice to confirm germline transmission. Resulting Hif2aG536W mice were then crossed to the C57BL/6-Gt(ROSA)26Sortm16(Cre)Arte mouse line to remove the floxed neomycin cassette. The Cre recombinase allele was removed through selective breeding to C57BL/6 mice. The Hif2aG536W mouse line was further backcrossed to C57BL/6J for at least 3 generations by the donating laboratory. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.


Disclaimer: If MMRRC Strain Genetic Quality Control (GQC; based on MiniMUGA genotyping and analysis) has been completed for this strain, the information might differ from the genetic background information provided by the submitter. MiniMUGA genetic analysis is done on a strain’s tissue samples taken when archived by or ordered from the assigned MMRRC Center.

Colony and Husbandry Information

For more information about this colony's health status contact csmmrrc@jax.org
Coat Color
Black
Eye
Black
MMRRC Breeding System
Backcross
Generation
N/A
Overall Breeding Performance
Excellent
Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: No No
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: 10 to 12 months Greater than 12 months
Average litter size
4 to 6
Recommended wean age
3 Weeks
Average Pups Weaned
4 to 6

Order Information

Limited quantities of breeder mice (up to 2 males and 2 females or 4 mice) per investigator per month are available from a live colony, usually available to ship in under 12 weeks. Larger quantities may be available, please contact the distributing center directly at csmmrrc@jax.org for more details.

Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

The donor or their institution limits the distribution to non-profit institutions only.

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*
Units Notes
075769-JAX-HET-F
075769-JAX-HET-M
075769-JAX-WT-F
075769-JAX-WT-M
Heterozygous / Hemizygous Female
Heterozygous / Hemizygous Male
Wild Type Female
Wild Type Male
$229.00 / Non-Profit Per Mouse The csmmrrc@jax.org may assess additional fees for any special requests (e.g., specific age or weight of mice, etc.).
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

Some MMRRC strains were submitted by the donor as cryopreserved germplasm, and because these strains were not cryopreserved by the MMRRC, we have not assessed the quality, nor genotype, of this material. Our expertise in reviving mice from various qualities of frozen sperm and embryos, using methods like IVF and ICSI, gives us confidence in successful recoveries in most cases. However, due to the uncertain quality of these samples, we'll limit revival attempts to two per order. Additional attempts are available for a fee, on top of standard charges, if requested. It's important to note that some strains may lack the expected mutation, so we can't assure successful order fulfillment until we attempt to revive the strain.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.