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- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Strain Information
Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Donating Investigator Dr. David Russell, Univ of Texas Southwest Med Ctr Dallas Description
Mice homozygous for the Epas1tm1Rus targeted mutation develop normally until embryonic day 11.5. Beginning at embryonic day 12.5 the ratio of homozygous embryos begins to decline and by day 16.5 there are no viable mutant embryos. Overall morphological development, including the circulatory system, is normal. Of particular interest however, is a pronounced bradycardia in homozygous mutant mice. Catecholamine levels in homozygous mutant mice are also significantly lower than wildtype controls. Administration of the catecholamine precursor DOPS to pregnant females rescues approximately 40% of mutant embryos. Embryos that survive to birth appear runted, fail to nurse, and die within 24 hours of birth. These results suggest a pivotal role of EPAS1 in catecholamine homeostasis. Heterozygous mice from this strain contain a modified lacZ gene in the targeting construct. This characteristic makes this strain useful as a marker for endothelial cells.Development
Disruption of the Epas1 gene was accomplished by homologous recombination in embryonic stem cells with a targeting plasmid in which a modified form of E. coli beta-galactosidase was substituted for exon 2 of the Epas1 gene.
Control Information
| Control | ||
|---|---|---|
| See control note: | Wildtype mice from the colony or B6129SF2 mice (Stock No. 101045) may be used as controls. The B6129SF2 mice only provide an approximate genetic match to this B6,129 background. | |
| Considerations for Choosing Controls | ||
Related Strains
lacZ Expression Strains
View lacZ Expression Strains (255 strains)
008407 STOCK Epas1tm1Mcs/J
Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Erythrocytosis, Familial, 4; ECYT4 (EPAS1)
assigned by genotype
Epas1tm1Rus/Epas1tm1Rus
either: (involves: 129S7/SvEvBrd) or (involves: 129S7/SvEvBrd * C57BL/6)
- mortality/aging
- complete lethality throughout fetal growth and development
- no homozygotes are obtained by E16.5; embryos surviving between E12.5 and E15.5 appear grossly normal with no overt morphological defects (MGI Ref ID J:50964)
- administration of catecholamine precursor DOPS to pregnant females prevents midgestational lethality in ~40% of mutant embryos, whereas L-DOPA fails to do so (MGI Ref ID J:50964)
- rescued pups are carried to term, but appear runted, fail to suckle, and die within 24 hr after birth (MGI Ref ID J:50964)
- partial embryonic lethality during organogenesis
- starting at E12.5, homozygous mutant embryos are obtained at a progressively declining Mendelian frequency (MGI Ref ID J:50964)
- cardiovascular system phenotype
- congestive heart failure (MGI Ref ID J:50964)
- decreased heart rate
- at E12.5, homozygotes exhibit significant bradycardia (average heart rate 26.9 +/- 8.0 beats per minute) relative to wild-type embryos (36.0 +/- 6.6 beats per minute) (MGI Ref ID J:50964)
- visceral vascular congestion
- homeostasis/metabolism phenotype
- decreased circulating noradrenaline level
- at E12.5, homozygotes exhibit significantly reduced noradrenaline levels (3.21 +/- 0.76 ng/mg protein) relative to wild-type embryos (5.42 +/- 2.15 ng/mg protein) (MGI Ref ID J:50964)
- liver/biliary system phenotype
- liver vascular congestion
- dead homozygotes exhibit congestion of blood in the liver (MGI Ref ID J:50964)
This mouse can be used to support research in many areas including:
Epas1tm1Rus relatedDevelopmental Biology Research
Embryonic Lethality (Homozygous)
Research Tools
lacZ Expression
Cancer Research
endothelial cell marker for neovascularization
Cardiovascular Research
endothelial cell marker (lacZ) for neovascularization
endothelial cell marker for neovascularization
Developmental Biology Research
Genetics Research
Tissue/Cell Markers
Tissue/Cell Markers: endothelial cell markers for neovascularization
Tissue/Cell Markers: endothelial cells
Cancer Research
Genes Regulating Growth and Proliferation
Cardiovascular Research
Heart Abnormalities
bradycardia
Hypertension
Hypotension
Cell Biology Research
Genes Regulating Growth and Proliferation
Developmental Biology Research
Embryonic Lethality (Homozygous)
Postnatal Lethality
Homozygous
Internal/Organ Research
Adrenal Medulla Defects
Heart Abnormalities
bradycardia
Other Organ Defects
Zuckerkanl
Research Tools
Cancer Research
endothelial cell marker for neovascularization
Cardiovascular Research
endothelial cell marker (lacZ) for neovascularization
Genetics Research
Tissue/Cell Markers
Tissue/Cell Markers: endothelial cells
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Epas1tm1Rus | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, David W Russell | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | Epas1-; HIF2alphaLacZ; | ||
| Mutation Made By | Dr. Hui Tian, Harvard University | ||
| Strain of Origin | 129S7/SvEvBrd | ||
| ES Cell Line Name | JH1 | ||
| ES Cell Line Strain | 129S7/SvEvBrd | ||
| Site of Expression | Targeting construct includes modified lacZ. Useful as a marker for endothelial cells in heterozygotes. | ||
| Expressed Gene | lacZ, beta-galactosidase, E. coli | ||
| Molecular Note | A lacZ gene was inserted and fused in-frame into exon 2, and was followed by a neomycin selection cassette. Western blot analysis indicated that the expression of wild-type transcript was eliminated from this allele. However, a beta-galactosidase fusionprotein was expressed under the control of the endogenous promoter. [MGI Ref ID J:50964] | ||
| Gene Symbol and Name | Epas1, endothelial PAS domain protein 1 | ||
| Chromosome | 17 | ||
| Gene Common Name(s) | ECYT4; HIF-2alpha; HIF2A; HLF; HRF; Hif like protein; MOP2; PASD2; bHLHe73; hypoxia inducible transcription factor 2alpha; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Epas1tm1Rus, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Tian H; Hammer RE; Matsumoto AM; Russell DW; McKnight SL. 1998. The hypoxia-responsive transcription factor EPAS1 is essential for catecholamine homeostasis and protection against heart failure during embryonic development. Genes Dev 12(21):3320-4. [PubMed: 9808618] [MGI Ref ID J:50964]
Additional References
Epas1tm1Rus relatedDing K; Scortegagna M; Seaman R; Birch DG; Garcia JA. 2005. Retinal Disease in Mice Lacking Hypoxia-Inducible Transcription Factor-2{alpha}. Invest Ophthalmol Vis Sci 46(3):1010-6. [PubMed: 15728559] [MGI Ref ID J:96396]
Dioum EM; Chen R; Alexander MS; Zhang Q; Hogg RT; Gerard RD; Garcia JA. 2009. Regulation of hypoxia-inducible factor 2alpha signaling by the stress-responsive deacetylase sirtuin 1. Science 324(5932):1289-93. [PubMed: 19498162] [MGI Ref ID J:149437]
Dioum EM; Clarke SL; Ding K; Repa JJ; Garcia JA. 2008. HIF-2alpha-haploinsufficient mice have blunted retinal neovascularization due to impaired expression of a proangiogenic gene battery. Invest Ophthalmol Vis Sci 49(6):2714-20. [PubMed: 18281611] [MGI Ref ID J:136883]
Hirata M; Kugimiya F; Fukai A; Saito T; Yano F; Ikeda T; Mabuchi A; Sapkota BR; Akune T; Nishida N; Yoshimura N; Nakagawa T; Tokunaga K; Nakamura K; Chung UI; Kawaguchi H. 2012. C/EBPbeta and RUNX2 cooperate to degrade cartilage with MMP-13 as the target and HIF-2alpha as the inducer in chondrocytes. Hum Mol Genet 21(5):1111-23. [PubMed: 22095691] [MGI Ref ID J:180600]
Ivey KN; Sutcliffe D; Richardson J; Clyman RI; Garcia JA; Srivastava D. 2008. Transcriptional regulation during development of the ductus arteriosus. Circ Res 103(4):388-95. [PubMed: 18635823] [MGI Ref ID J:152650]
Oktay Y; Dioum E; Matsuzaki S; Ding K; Yan LJ; Haller RG; Szweda LI; Garcia JA. 2007. Hypoxia-inducible factor 2alpha regulates expression of the mitochondrial aconitase chaperone protein frataxin. J Biol Chem 282(16):11750-6. [PubMed: 17322295] [MGI Ref ID J:121138]
Saito T; Fukai A; Mabuchi A; Ikeda T; Yano F; Ohba S; Nishida N; Akune T; Yoshimura N; Nakagawa T; Nakamura K; Tokunaga K; Chung UI; Kawaguchi H. 2010. Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development. Nat Med 16(6):678-86. [PubMed: 20495570] [MGI Ref ID J:161526]
Scortegagna M; Ding K; Oktay Y; Gaur A; Thurmond F; Yan LJ; Marck BT; Matsumoto AM; Shelton JM; Richardson JA; Bennett MJ; Garcia JA. 2003. Multiple organ pathology, metabolic abnormalities and impaired homeostasis of reactive oxygen species in Epas1-/- mice. Nat Genet 35(4):331-40. [PubMed: 14608355] [MGI Ref ID J:86736]
Scortegagna M; Ding K; Zhang Q; Oktay Y; Bennett MJ; Bennett M; Shelton JM; Richardson JA; Moe O; Garcia JA. 2005. HIF-2alpha regulates murine hematopoietic development in an erythropoietin-dependent manner. Blood 105(8):3133-40. [PubMed: 15626745] [MGI Ref ID J:98454]
Scortegagna M; Morris MA; Oktay Y; Bennett M; Garcia JA. 2003. The HIF family member EPAS1/HIF-2alpha is required for normal hematopoiesis in mice. Blood 102(5):1634-40. [PubMed: 12750163] [MGI Ref ID J:85299]
Steenhard BM; Freeburg PB; Isom K; Stroganova L; Borza DB; Hudson BG; St John PL; Zelenchuk A; Abrahamson DR. 2007. Kidney development and gene expression in the HIF2alpha knockout mouse. Dev Dyn 236(4):1115-1125. [PubMed: 17342756] [MGI Ref ID J:119808]
Yang S; Kim J; Ryu JH; Oh H; Chun CH; Kim BJ; Min BH; Chun JS. 2010. Hypoxia-inducible factor-2alpha is a catabolic regulator of osteoarthritic cartilage destruction. Nat Med 16(6):687-93. [PubMed: 20495569] [MGI Ref ID J:161527]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $1980.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2574.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
General Supply Notes
- Genomic DNA is available for this strain from the Mouse DNA Resource.
Control Information
| Control | ||
|---|---|---|
| See control note: | Wildtype mice from the colony or B6129SF2 mice (Stock No. 101045) may be used as controls. The B6129SF2 mice only provide an approximate genetic match to this B6,129 background. | |
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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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
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| phone: | 207-288-6470 |
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