B6;129S7-Epas1^tm1Rus/J

Stock number: 003266
Product name: EPAS1 KO
Research areas: Cancer Research, Cardiovascular Research, Cell Biology Research, Developmental Biology Research, Internal/Organ Research, Research Tools

Description

These Epas1 knock-out mice exhibit bradycardia and reduced catecholamine levels.

Detailed description

Mice homozygous for the Epas1^tm1Rus 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 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.

Allele

Symbol: Epas1^tm1Rus
Name: targeted mutation 1, David W Russell
MGI accession ID: MGI:1861921
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Epas1
Marker name: endothelial PAS domain protein 1
Chromosome: 17
Strain of origin: 129S7/SvEvBrd
Expressed genes: lacZ,beta-galactosidase,E. coli
Site of expression: Targeting construct includes modified lacZ. Useful as a marker for endothelial cells in heterozygotes.
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.