This Hpx knockout strain is useful in studies of oxidative stress, iron metabolism, myelination, and intravascular hemolysis.
Emanuela Tolosano, University of Torino
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Reporter, Null/Knockout) | Hpx | hemopexin |
The targeted Hpx hemopexin gene encodes a plasma glycoprotein that has a high binding affinity to heme, scavenges and transports free heme, and is involved in heme/iron homeostasis.
These knock-out mice carry an allele in which a lacZ-PGKneo cassette was inserted into the ATG start codon in exon 1.
Mice that are homozygous for the targeted mutation are viable and fertile.
No gene product (mRNA) is detected by Northern blot analysis of liver from homozygotes.
β-galactosidase activity is detected in hepatocytes, ependymal
cells and choroid plexi.
Mutant homozygous mice recover more slowly from experimentally induced acute hemolysis, exhibiting protracted increased levels of plasma haptoglobin, renal iron, urine hemoglobin, and renal damage.
Homozygotes have an earlier onset and more severe response to experimental autoimmune encephalomyelitis (EAE) due to increased production of Th17 cells.
Iron levels in duodenal enterocytes are higher in homozygotes.
Null mice on the 129Sv genetic background show an
increase in the number of iron-loaded oligodendrocytes in the basal ganglia and thalamus, and exhibit impaired
myelination of the cerebral cortex. The response to heme overload in homozygotes includes heme accumulation and
oxidative stress in vascular endothelium and in macrophages compared to wildtype controls, increased vascular
permeability as well as red blood cell congestion in liver sinusoids.
A targeting vector containing a LacZ-PGKneo cassette was inserted into the ATG start codon to disrupt exon 1. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1- Kitl+-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric male animals were crossed to C57BL/6 female mice, and then backcrossed to C57BL/6J for at least 8 generations by the donating lab (see SNP note below). Heterozygotes were then intercrossed to generate homozygotes. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).
A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 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. One the 43 markers throughout the genome was segregating with 129, and 3 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.
Expressed Gene | lacZ, beta-galactosidase, E. coli |
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Site of Expression | Β-galactosidase is expressed in hepatocytes, ependymalcells and choroid plexi. |
Allele Name | targeted mutation 1, Fiorella Altruda |
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Allele Type | Targeted (Reporter, Null/Knockout) |
Allele Synonym(s) | Hx- |
Gene Symbol and Name | Hpx, hemopexin |
Gene Synonym(s) | |
Expressed Gene | lacZ, beta-galactosidase, E. coli |
Site of Expression | Β-galactosidase is expressed in hepatocytes, ependymalcells and choroid plexi. |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 7 |
Molecular Note | The gene was disrupted by insertion of a lacZ-neo cassette into the ATG start site of exon 1. Absence of gene expression in homozygous animals was confirmed by Northern blot analysis of total liver RNA. X-gal staining showed expression of lacZ in liver sections from mutant animals. |
When maintaining a live colony, these mice can be bred as homozygotes.
When using the Hx KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #029380 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Hpx<tm1Altr> |
Frozen Mouse Embryo | B6.129-Hpx<tm1Altr>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129-Hpx<tm1Altr>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129-Hpx<tm1Altr>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6.129-Hpx<tm1Altr>/J Frozen Embryo | $3373.50 |
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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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