B6(Cg)-Egln1^{tm3.1(EGLN1)Fsl}/Mmjax

Stock number: 040414
Product name: Phd2^WT
Research areas: Cardiovascular Research, Cell Biology Research, Hematological Research

Description

Phd2^WT knock-in (KI) mice have endogenous exon 1 of the Egln1 gene replaced with human wildtype sequence. This mouse line may be useful as a control to the Phd2^Tib mouse line (RRID:MMRRC_075764-JAX) when studying oxygen-sensing and the hypoxia-inducible factor (HIF) pathway.

Detailed description

Prolyl hydroxylase domain protein 2 (PHD2), coded by Egln1, is a protein that plays a crucial role in regulating oxygen levels in the body by hydroxylating hypoxia-inducible factor alpha (HIF-α), which is a subunit of the hypoxia-inducible factor (HIF) complex. HIF is necessary for oxygen homeostasis by regulating metabolic adaptation, erythropoiesis (red blood cell production), respiration, and angiogenesis. These Phd2^WT mice have a humanized exon 1 replacing endogenous exon 1 of the Egln1 gene.

Homozygous mice are viable and fertile with no overt phenotype. Phd2^WT may be useful as a control to the Phd2^Tib mouse line (RRID:MMRRC_075764-JAX) when studying oxygen-sensing and the hypoxia-inducible factor (HIF) pathway.

Development

The Phd2^WT targeting vector was designed by replacing the endogenous exon 1 of the egl-9 family hypoxia-inducible factor 1 (Egln1) gene, with human exon 1 sequence. The targeting construct also contains a loxP-flanked neomycin selection cassette. The construct was electroporated into C57BL/6-derived EAP6 embryonic stem (ES) cells and correctly targeted ES cells were injected into recipient blastocysts. Chimeric mice were bred to B6(Cg)-Tyr^c-2J/J mice to confirm germline transmission. Resulting Phd2^WT mice were then crossed to the C57BL/6-Gt(ROSA)26Sor^{tm16(Cre)Arte} mouse line to remove the floxed neomycin cassette. The Cre recombinase allele was removed through selective breeding to C57BL/6J mice. The Phd2^WT mouse line was maintained on a C57BL/6 background by the donating laboratory. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

Allele

Symbol: Egln1^{tm3.1(EGLN1)Fsl}
Name: targeted mutation 3.1, Frank Lee
MGI accession ID: MGI:8175683
Generation method: Targeted
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: Phd2^Hum; Phd2^wt
Marker symbol: Egln1
Marker name: egl-9 family hypoxia-inducible factor 1
Marker synonyms: C1orf12; ECYT3; HALAH; Hif-p4h-2; HIFPH2; HIF-PH2; HPH2; HPH-2; ORF13; PHD2; PHD-2; SM20; SM-20; ZMYND6
Chromosome: 8
Strain of origin: C57BL/6
Molecular note: The targeting vector was designed to replace the endogenous exon 1 of the egl-9 family hypoxia-inducible factor 1 (Egln1) gene with the human exon 1 sequence. The targeting construct also consisted of a loxP-flanked neomycin selection cassette. The the floxed neomycin cassette was removed by Cre recombinase.