These Epas1 knock-out mice exhibit bradycardia and reduced catecholamine levels.
Dr. David Russell, Univ of Texas Southwest Med Ctr Dallas
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Reporter, Null/Knockout) | Epas1 | endothelial PAS domain protein 1 |
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.
Disruption of the Epas1 gene was accomplished by homologous recombination in 129S7/SvEvBrd-derived JH1 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. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6.
Expressed Gene | lacZ, beta-galactosidase, E. coli |
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Site of Expression | Targeting construct includes modified lacZ. Useful as a marker for endothelial cells in heterozygotes. |
Allele Name | targeted mutation 1, David W Russell |
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Allele Type | Targeted (Reporter, Null/Knockout) |
Allele Synonym(s) | Epas1-; HIF2alphaLacZ |
Gene Symbol and Name | Epas1, endothelial PAS domain protein 1 |
Gene Synonym(s) | |
Expressed Gene | lacZ, beta-galactosidase, E. coli |
Site of Expression | Targeting construct includes modified lacZ. Useful as a marker for endothelial cells in heterozygotes. |
Strain of Origin | 129S7/SvEvBrd |
Chromosome | 17 |
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 fusion protein was expressed under the control of the endogenous promoter. |
Mutations Made By | Dr. Hui Tian, Harvard University |
The strain is maintained by heterozygote matings. Homozygotes die mid-gestation.
When using the EPAS1 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #003266 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or Wild-type for Epas1<tm1Rus> |
Frozen Mouse Embryo | B6;129S7-Epas1<tm1Rus>/J | $2595.00 |
Frozen Mouse Embryo | B6;129S7-Epas1<tm1Rus>/J | $2595.00 |
Frozen Mouse Embryo | B6;129S7-Epas1<tm1Rus>/J | $3373.50 |
Frozen Mouse Embryo | B6;129S7-Epas1<tm1Rus>/J | $3373.50 |
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