These mice carry a targeted mutation of Hfe, hemochromatosis, exhibit iron loading, and have applications in studies of hereditary hemochromatosis, iron homeostasis and innate immune response.
Nancy C. Andrews, Duke University School of Medicine
Genetic Background | Generation |
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N10pN1+F11
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Hfe | hemochromatosis |
Starting at:
$278.00 Domestic price for female |
$2,854.50 Domestic price Cryo Recovery |
Hfe, hemochromatosis, is involved in regulation of intestinal iron absorption. Mice that are homozygous for this targeted mutation are viable, fertile, normal in size and recapitulate human hereditary hemochromatosis. Hereditary hemochromatosis is a genetic disorder of iron hyperabsorption that results in hyperferremia and iron loading in tissues. By 4 weeks of age, homozygotes on the 129S6/SvEvTac background display elevated blood iron levels and up to 2.2-fold higher hepatic nonheme iron than controls. At 10 weeks of age, homozygotes on the 129S6/SvEvTac background have up to 3.3-fold higher hepatic nonheme iron than controls. Iron loading is less severe in homozygotes on the C57BL/6J background. Heterozygotes exhibit some iron loading. Macrophages isolated from homozygotes have impaired TLR4/TRAM/TRIF pathway signalling, with reduced production of TNF-alpha and IL-6. When challenged with Salmonella typhimurium induced enterocolitis, homozygotes exhibit a less severe inflammatory response. Expression of Hamp (hepcidin antimicrobial peptide) is reduced in homozygotes. The Donating Investigator notes that the level of iron loading in mutant animals varies based on the iron content of the diet, breeding strategy, and other factors.
A targeting vector containing a floxed NEO/cytosine deaminase cassette was used to replace part of exon 3 and all of exon 4. The construct was electroporated into 129S6/SvEvTac derived TC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6J for more than 10 generations.
Allele Name | targeted mutation 2, Nancy C Andrews |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Hfe- |
Gene Symbol and Name | Hfe, hemochromatosis |
Gene Synonym(s) | |
Strain of Origin | 129S6/SvEvTac |
Chromosome | 13 |
Molecular Note | A LoxP site flanked neomycin resistance gene cassette replaced a segment of genomic sequence starting in exon 3 and ending in intron 4. |
Mutations Made By | Nancy Andrews, Duke University School of Medicine |
When maintaining a live colony, these mice can be bred as homozygotes.
When using the Hfe- mouse strain in a publication, please cite the originating article(s) and include JAX stock #017784 in your Materials and Methods section.
Service/Product | Description | Price |
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Heterozygous for Hfe<tm2Nca> |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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