Of note, hHGFki;scid mice also harboring the Il2Rγcnull mutation on the NOD-congenic background are available: NSG-hHGFki (Stock No. 014553).
These hHGFki;scid mice harbor the "humanized" knock-in mutation (hHGFki) that replaces the mouse hepatocyte growth factor (HGF) coding factor, and the Prkdcscid mutation that results in T- and B-cell deficiency. These mice may be useful in studying the HGF/MET pathway in human tumor xenografts and mouse tumor allografts.
William M Rideout III, AVEO Pharmaceuticals, Inc
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Spontaneous | Prkdc | protein kinase, DNA activated, catalytic polypeptide |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Inserted expressed sequence, Humanized sequence) | Hgf | hepatocyte growth factor |
Of note, hHGFki;scid mice also harboring the Il2Rγcnull mutation on the NOD-congenic background are available: NSG-hHGFki (Stock No. 014553).
Mice homozygous for both the hHGFki and Prkdcscid alleles, also called immunocompromised hHGFki mice, are viable and fertile.
The hHGFki allele is a "humanized" knock-in mutation that replaces the mouse hepatocyte growth factor (HGF) coding region downstream of the signal sequence with the human HGF cDNA sequence. As a result, the endogenous mouse promoter drives expression of human HGF. While the human HGF activates both the human and murine form of its tyrosine kinase receptor (met proto-oncogene (MET; c-Met)), the murine HGF is unable to activate human MET. Mice homozygous for hHGFki express only the human form of HGF. In homozygous hHGFki mice, HGF expression from the knock-in allele is observed in developing embryo, as well as adult liver, kidney and lung. hHGFki homozygous mice exhibit an increase in serum HGF after clotting.
Mice homozygous for the Prkdcscid mutation exhibit T- and B-cell deficiency.
A targeting vector was designed to replace exons 3-6 of the mouse hepatocyte growth factor (Hgf) locus with a cDNA sequence encoding exons 2-18 of the human hepatocyte growth factor (HGF), a polyA signal, and a frt-flanked PGK-neo cassette. The construct was electroporated into 129S6/SvEvTac-derived JB26A10 embryonic stem (ES) cells. Next, ES cells were transiently transfected with a FLPe expressing plasmid to remove the frt-flanked PGK-neo cassette. Correctly targeted ES cells were then injected into recipient blastocysts and chimeric mice were bred with C57BL/6 mice to establish the hHGFki colony. The hHGFki mice were then bred with C3Hscid (C3SnSmn.CB17-Prkdcscid/J ; see Stock No. 001131) to generate the hHGFki;scid double mutant mice. Mice homozygous for both alleles were bred together for many generations prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred together and/or with C3SnSmn.CB17-Prkdcscid/J ; see Stock No. 001131) for at least one generation to establish the colony. After this, mice homozygous for both alleles were bred together to maintain the colony.
Expressed Gene | HGF, hepatocyte growth factor, human |
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Site of Expression |
Allele Name | severe combined immunodeficiency |
---|---|
Allele Type | Spontaneous |
Allele Synonym(s) | SCID |
Gene Symbol and Name | Prkdc, protein kinase, DNA activated, catalytic polypeptide |
Gene Synonym(s) | |
Site of Expression | T and B lymphocytes. |
Strain of Origin | C.BKa-Ighb/Icr |
Chromosome | 16 |
Molecular Note | A T-to-A transversion point mutation at a position corresponding to codon 4046 (codon 4095 in transcript ENSMUST00000023352.8) created a premature stop codon (p.Y4046*). |
Allele Name | targeted mutation 1.1, AVEO Pharmaceuticals Inc |
---|---|
Allele Type | Targeted (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | hHGFki |
Gene Symbol and Name | Hgf, hepatocyte growth factor |
Gene Synonym(s) | |
Expressed Gene | HGF, hepatocyte growth factor, human |
Strain of Origin | 129S6/SvEvTac |
Chromosome | 5 |
General Note | ES cells = JB26A10 (129S6/SvEvTac) |
Molecular Note | A targeting vector was designed to replace exons 3-6 of the mouse hepatocyte growth factor (Hgf) locus with a cDNA sequence encoding exons 2-18 of the human hepatocyte growth factor (HGF), a polyA signal, and a frt-flanked PGK-neo cassette. Flp-mediated recombination removed the neo cassette. |
When maintaining a live colony, mice homozygous for the hHGFki allele and homozygous for the Prkdcscid allele may be bred together. There are no special husbandry requirements other than those necessary for immunocompromised Prkdcscid mice.
When using the hHGFki;scid mouse strain in a publication, please cite the originating article(s) and include JAX stock #014543 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Hgf<tm1.1(HGF)Aveo>, Homozygous for Prkdc<scid>. Minimum of 1 pair provided |
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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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