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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
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Description
Strain Information
Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Donating Investigator 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
| 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 (178 strains)
008407 STOCK Epas1tm1Mcs/J
Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
assigned by genotype
Epas1tm1Rus/Epas1tm1Rus
either: (involves: 129S7/SvEvBrd) or (involves: 129S7/SvEvBrd * C57BL/6)
- lethality-prenatal/perinatal
- embryonic lethality during organogenesis (MGI Ref ID J:50964)
- starting at E12.5, homozygous mutant embryos are obtained at a progressively declining Mendelian frequency
- lethality throughout fetal growth and development (MGI Ref ID J:50964)
- no homozygotes are obtained by E16.5; embryos surviving between E12.5 and E15.5 appear grossly normal with no overt morphological defects
- administration of catecholamine precursor DOPS to pregnant females prevents midgestational lethality in ~40% of mutant embryos, whereas L-DOPA fails to do so
- rescued pups are carried to term, but appear runted, fail to suckle, and die within 24 hr after birth
- cardiovascular system phenotype
- congestive heart failure (MGI Ref ID J:50964)
- decreased heart rate (MGI Ref ID J:50964)
- at E12.5, homozygotes exhibit significant bradycardia (average heart rate 26.9 ± 8.0) relative to wild-type embryos (36.0 ± 6.6)
- vasculature congestion (MGI Ref ID J:50964)
- dead homozygotes exhibit congestion of blood in the liver and cardiac outflow tracts; however, no morphological defects are noted in the heart, liver, or placenta at E11.5 or E15.5
- homeostasis/metabolism phenotype
- decreased circulating noradrenaline level (MGI Ref ID J:50964)
- 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)
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)
Cardiovascular Research (endothelial cell marker for neovascularization)
Developmental Biology Research
Genetics Research (Tissue/Cell Markers: endothelial cell markers for neovascularization)
Genetics Research (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 Mortality (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: endothelial cells)
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Epas1tm1Rus | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, David W Russell | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | Epas1-; HIF2alphaLacZ; | ||
| Mutation Made By | 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. | ||
| 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 | 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] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Epas1tm1Rus, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
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; 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]
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]
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]
Health & husbandry
Health & Colony Maintenance Information
Currently there no information available for this strain. This may be due to the supply level of this strain.
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
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*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
Additional Supply Details
| Pricing for International shipping destinations |
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*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
Additional Supply Details
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Supply Details
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
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| Supply Notes |
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Control Information
| 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 | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
General Terms and Conditions
See Terms of Use
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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 and Purchasing Information
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