HIF1αflox mice have loxP sites flanking exon 2 of the hypoxia inducible factor 1, alpha subunit gene (Hif1a). Exposure to Cre recombinase removes the floxed sequence - creating a null allele. Mice from this strain can be crossed to strains expressing Cre recombinase in various tissues and may be useful for studies of the role of HIF transcription factors in von Hippel-Landau syndrome, adult erythropoiesis, inflammation, mammary epithelium, tumor angiogenesis, and lung development as examples.
Randall Johnson, UC-San Diego
These HIF1αflox mice possess loxP sites on either side of exon 2 of the targeted gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 2 deleted in the cre-expressing tissue(s).
For example, when crossed to a strain expressing Cre recombinase in skeletal and cardiac muscle (see Stock No. 006475), this mutant mouse strain may be useful in studies of the metabolic control of muscle function.
When bred to a strain with the targeted null allele in von Hippel-Lindau syndrome homolog, Vhlh (Stock No. 004081) and a strain expressing Cre recombinase in liver (Stock No. 003574), this mutant mouse strain may be useful in the role of HIF transcription factors in von Hippel-Landau syndrome.
When crossed to a tamoxifen inducible strain with widespread Cre recombinase expression (see Stock No. 008085), this mutant mouse strain may be useful in studies of adult erythropoiesis.
When bred to a strain expressing Cre recombinase in the myeloid cell lineage (see Stock No. 004781 for example), this mutant mouse strain may be useful in studies of inflammation.
When bred to a strain expressing Cre recombinase in the mammary gland and other secretory tissues (see Stock No. 003551 for example), this mutant mouse strain may be useful in studies of mammary epithelium.
When bred to a strain expressing Cre recombinase in vascular endothelial cells (see Stock No. 008863 for example), this mutant mouse strain may be useful in studies of tumor angiogenesis.
When bred to a strain expressing Cre recombinase under the control of a tetracycline-responsive promoter element and a strain expressing a tetracycline-controlled activator protein in lung epithelial cells (see Stock No. 006234 and 006235 respectively), this mutant mouse strain may be useful in studies of lung development.
Similarly oriented loxP sites were placed upstream of exon 2 and flanking the neomycin resistance cassette (located in intron 2). The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a cre expression plasmid for the purpose of removing the selectable marker cassette. ES cells that had successfully undergone Cre-mediated recombination and no longer retained the cassette but did retain the loxP flanked exon 2 were injected in C57BL/6 blastocysts. The donating investigator reported that the resulting chimeric male animals were backcrossed to wildtype C57BL/6J mice (see SNP note below) for 12 generations. A speed congenic protocol was used for the first 6 generations of backcrossing, after which the mice were backcrossed an additional 6 generations to C57BL/6J (see SNP note below) prior to arriving at The Jackson Laboratory. The Y chromosome may not have been fixed to the C57BL/6J genetic background.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, at least 2 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||targeted mutation 3, Randall S Johnson|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||+f; Hif+f; Hiff; Hif1a2lox; HIF1af+; Hif1afl; Hif1aloxP; Hif-1alpha 2-lox; HIF-1alpha+f; HIF-1alphaF; HIF1alphaflox; I.1-lox|
|Gene Symbol and Name||Hif1a, hypoxia inducible factor 1, alpha subunit|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||A loxP site was inserted in intron 1 and a floxed neomycin resistance cassette was placed in intron 2. Exon 2 was left flanked by loxP sites after the neo cassette was excised by in vitro expression of cre recombinase.|
|Mutations Made By|| |
Randall Johnson, UC-San Diego
When maintaining a live colony, these mice are bred as homozygotes.
When using the HIF1αflox mouse strain in a publication, please cite the originating article(s) and include JAX stock #007561 in your Materials and Methods section.