The Gpx4f allele has loxP sites flanking exons 2- 4 of the glutathione peroxidase 4 gene. Removal of the floxed sequence creates a null allele. Homozygous knockout mice exhibit mitochondrial dysfunction, increased apoptosis and neurodegeneration.
Qitao Ran, UT Health Science at San Antonio
The Gpx4f allele has loxP sites flanking exons 2-4 of the glutathione peroxidase 4 (Gpx4) gene.
Gpx4 encodes a member of the selenoprotein glutathione peroxidase family that functions to reduce hydroperoxides in membrane lipids and lipoproteins, thus protecting mitochondrial function and suppressing apoptosis.
Mice homozygous for the floxed allele are viable and fertile with no reported abnormalities.
When bred to mice that express a tamoxifan-inducible Cre recombinase, the resulting offspring may be useful in generating an inducible Gpx4 knockout.
For example, when bred to Gt(ROSA)26Sortm1(cre/ERT)Nat
Cre-expressing mice (Stock No. 004847) the resulting Gpx4 knockout homozygotes die within 2 weeks. Mice exhibit increased mitochondrial damage, decreased electron transport complex activity, reduced liver ATP production, increased apoptosis, neuronal loss, and increased astrogliosis.
The targeting vector was designed to insert a loxP site followed by a FRT-flanked neomycin cassette upstream of exon 2 and a second loxP site downstream of exon 4. The construct was electroporated into 129S6/SvEvTac-derived W4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice. Offspring were bred with B6.Cg-Tg(ACTFLPe)9205Dym/J (Stock No. 005703)
to delete the neo cassette. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 1.1, Qitao Ran|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Gpx4, glutathione peroxidase 4|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||A loxP site and FRT flanked neo cassette were inserted upstream of exon 2 and a loxP site was inserted downstream of exon 4 via homologous recombination. Flp mediated recombination removed the neo cassette leaving exons 2 - 4 floxed.|
While maintaining a live colony, these mice are bred as homozygotes.
When using the Gpx4f mouse strain in a publication, please cite the originating article(s) and include JAX stock #027964 in your Materials and Methods section.