These NGFI-B or Nur77 mutant mice are on a congenic FVB/N background and may be useful in studies related to tumor growth, wound healing, angiogenesis and inflammation. Although the original analysis of this allele revealed no detectable
transcript of any type from this gene in the thymus, findings by Koenis,
2018 (PMID 30111591)
indicate the presence of a transcript capable of producing a truncated
N-terminal domain (NTD) peptide that can stabilize and activate HIF1A (hypoxia inducible factor 1, alpha subunit).
Huiyan Zeng, Beth Israel Deaconess Medical Center
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Not Specified) | Nr4a1 | nuclear receptor subfamily 4, group A, member 1 |
The orphan nuclear transcription factor encoded by the Nr4a1 gene is involved in neuron development & maintenance, myofiber size and muscle mass, wound healing, progesterone receptor-mediated permeability responses in uterine embryo implantation, angiogenesis, anti-inflammation, and glucose homeostasis. These NGFI-B or Nur77 mutant mice carry a targeted mutation in which a PGK-NEO cassette disrupts exon 2. Mice homozygous for the allele and on a congenic FVB/N background are viable and fertile. The Donating Investigator reports that the congenic FVB/N background does not alter the phenotype observed in B6;129 mixed and congenic C57BL/6 Nr4a1tm1Jmi mutant mice. On the C57BL/6 background, knock-out mice have greatly diminished angiogenic response to VEGF-A, histamine or serotonin induction, and are more susceptible to diet-induced obesity and insulin resistance.
Of note, although the original analysis of this allele revealed no detectable transcript of any type from this gene in the thymus, findings by Koenis, 2018 (PMID 30111591) indicate the presence of a transcript capable of producing a truncated N-terminal domain (NTD) peptide that can stabilize and activate HIF1A (hypoxia inducible factor 1, alpha subunit). Neither the transcriptional nor the translational start of the gene are disrupted.
A targeting vector was designed by Jeffrey Milbrandt (Washington University in St. Louis), to insert a phosphoglycerate kinase-neomycin resistance cassette (PGK-neo) cassette into the coding region of exon 2 of the Nr4a1 gene. This construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. Chimeric males were bred with C57BL/6J females to establish heterozygous mice. The mice were backcrossed to C57BL/6 for several generations. Dr. Huiyan Zeng obtained mice from Dr. Milbrandt and backcrossed the mice to FVB/N for 10 generations. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize FVB/NJ oocytes (Stock No. 001800).
Allele Name | targeted mutation 1, Jeffrey Milbrandt |
---|---|
Allele Type | Targeted (Not Specified) |
Allele Synonym(s) | classical Nur77-KO; NGFI-B (-); NGFI-B-; Nur77- |
Gene Symbol and Name | Nr4a1, nuclear receptor subfamily 4, group A, member 1 |
Gene Synonym(s) | |
Strain of Origin | 129S2/SvPas |
Chromosome | 15 |
Molecular Note | Exon 2 was disrupted by the insertion of a neomycin resistance gene 300 bp downstream of the translational start site. A functional portion of the N-terminal domain of the full length gene is expressed. |
When maintaining a live colony, these mice can be bred as homozygotes.
When using the Nur77-/-(Fvb) mouse strain in a publication, please cite the originating article(s) and include JAX stock #028205 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Nr4a1<tm1Jmi>/Hzeng |
Frozen Mouse Embryo | FVB.129S2(B6)-Nr4a1<tm1Jmi>/HzengJ Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | FVB.129S2(B6)-Nr4a1<tm1Jmi>/HzengJ Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | FVB.129S2(B6)-Nr4a1<tm1Jmi>/HzengJ Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | FVB.129S2(B6)-Nr4a1<tm1Jmi>/HzengJ 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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