HIF1 is a master regulator of homeostatic response to hypoxia. The Hif1a (hypoxia inducible factor 1, alpha subunit) knockout allele results in embryonic lethality by E11; embryos exhibit neural tube defects and cardiovascular malformations. On the diabetes-inducible FVB/N background, mice provide a tool for examining the role of hypoxia in diabetes.
Claudia Kappen, Pennington Biomedical Research Center
Hif1a (hypoxia inducible factor 1, alpha subunit) encodes the alpha subunit of a heterodimer that functions as a master regulator of homeostatic response to hypoxia. HIF1 is essential to embryonic vascularization, tumor angiogenesis and ischemic disease.
Loss of HIF1A results in embryonic lethality by E11. Beginning at E8.5, some Hif1a null embryos appear abnormal, however, by E9 all null embryos are morphologically abnormal. Abnormal embryos are characterized by mesenchymal cell death resulting in failure of neural tube closure with cystic degeneration and prolapse of neural folds, hyperplasia of the presumptive myocardium, anomalous vascular structures in the cephalic mesenchyme, absent or hypoplastic branchial arch vessels, and abnormal dorsal aortae. Hif1atm1Jhu embryonic stem cells have reduced mRNA levels of glucose transporters, glycolytic enzymes, and vascular endothelial growth factor as well as impaired cellular proliferation.
On the FVB/N background streptozotocin (STZ) administration induces diabetes in Hif1a null mice providing a resource for examining the role of hypoxia in diabetes.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
A targeting vector containing a neomycin resistance cassette was used to replace exon 2. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were bred to C57BL/6. Mice from the colony were transferred to Claudia Kappen at the Pennington Biomedical Research Institute and the allele was introgressed to FVB/N for at least 10 generations. Upon arrival, mice were bred to FVB/NJ for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 1, Johns Hopkins University|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Hif1a, hypoxia inducible factor 1, alpha subunit|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A neomycin resistance cassette replaced exon 2, which encodes the bHLH domain, of the gene.|
While maintaining a live colony, these mice are bred as heterozygotes. Mice homozygous for the mutation are not viable.
When using the Hif1a- mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #37489 in your Materials and Methods section.