These Hfe knock-out mice exhibit an elevation in plasma and hepatic iron concentration and an increase in levels of saturated transferrin.
Susan Gilfillan, Washington University School of Medicine
At birth, mice homozygous null for the Hfe gene are viable, normal in size and do not display any gross physical or behavioral abnormalities. Adult mice are fertile. Full-length Hfe transcripts are not detected in either liver or kidney tissue. A poorly expressed, alternate transcript resulting from a direct splicing event between exons 1 and 4 is detected. At twelve weeks of age, a significant elevation in plasma and hepatic iron concentration is evident as is an increase in levels of saturated transferrin. Excess iron stores may be the result of enhanced duodenal iron absorbtion. This strain represents a viable animal model of human hemochromatosis.
A targeting vector containing a loxP-flanked neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter was used to disrupt the second and third exons of the Hfe gene. The construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric male animals were backcrossed to C57BL/6 females.
|Allele Name||targeted mutation 1, Susan Gilfillan|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Hfe, hemochromatosis|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||2.5 kb of sequence containing the second and third exons, which encode the alpha1 and alpha2 putative ligand binding domains, were replaced with a floxed PGK neomycin selection cassette. Northern blots prepared with total RNA isolated from kidney and liver tissue did not detect full length mRNA in homozygous mutant mice.|
|Mutations Made By|| |
Seiamak Bahram, Centre de Rech d'Imm et d'Hematologie
This strain originated on a B6;129P2 background and has been backcrossed to C57BL/6 for at least eleven generations.(11/21/00)
When using the HFEo mouse strain in a publication, please cite the originating article(s) and include JAX stock #003812 in your Materials and Methods section.