Strain Name: |
FVB.129S6-Gt(ROSA)26Sortm1(HIF1A/luc)Kael/J |
|---|---|
Stock Number: |
006206 |
Availability: | Repository- Live |
General Terms and Conditions |
| Genes & Alleles | Gt(ROSA)26Sor; Gt(ROSA)26Sortm1(HIF1A/luc)Kael; |
Product Information
Strain Details
Type JAX® GEMM® Strain - Congenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Targeted Mutation Mating System Homozygote x Homozygote (Female x Male) Species laboratory mouse Donating Investigator William Kaelin, Dana Farber Cancer Institute Generation N7+N2 (03-DEC-07) Strain Description
Mice heterozygous for this "ODD-luc" knock-in are viable and fertile with no gross phenotypic or behavioral abnormalities. These mice have the C-terminal portion of the hypoxia-inducible factor 1 alpha (HIF1A) oxygen-dependent degradation domain (ODD) fused to the firefly luciferase (luc) gene. This region of the ODD also contains a proline residue (amino acid 564) that, when hydroxylated, will serve as a binding site for von Hippel-Lindau tumor suppressor protein (pVHL). Under normal oxygen concentrations, prolyl hydroxylation by egg-laying-defective nine (EGLN) proteins leads to pVHL-dependent polyubiquitylation and proteasomal degradation (thus, little or no luciferase fluorescence). Under hypoxia, proline hydroxylation is impaired and ubiquitination is attenuated, resulting in stabilization of the fusion protein and high levels of luciferase fluorescence in the hypoxic tissue(s). These "ODD-Luc" bioluminescent reporter mice may be useful in researching transcriptional regulation of hypoxia-inducible genes, cancer, ischemia, cardiovascular, myocardial infarction, stroke, pharmacokinetics, or other studies where imaging/reporting the development of tissue hypoxia and the action of small molecule inhibitors of HIF prolyl hydroxylase activity are appropriate.Strain Development
A fusion protein was created with a human hypoxia-inducible factor 1 alpha sequence coding for amino acids 530-652 (HIF1a [aa 530-652]; this includes the C-terminal portion of the oxygen-dependent degradation domain [ODD]) fused to the firefly luciferase (luc) gene. This “ODD-Luc” fusion protein was preceded by a loxP-flanked PGK-neo cassette and followed by a bovine polyadenylation stop sequence. This targeting construct was incorporated into the Gt(ROSA)26Sor locus via electroporation into 129S6/SvEvTac-derived TC1 embryonic stem (ES) cells. Correctly targeted ES cells were microinjected into C57BL/6 blastocysts. Chimeric mice were bred to EIIA-Cre transgenic mice (on the FVB genetic background) to remove a loxP-flanked neomycin cassette. The resulting mice (with a single loxP site ahead of the “ODD-Luc” fusion gene) were bred with wildtype FVB mice (and selected against the Cre transgene) for 6 generations prior to arrival at The Jackson Laboratory.
Mammalian Phenotype Terms assigned by genotype |
Gene & Allele Details
| Allele Symbol | Gt(ROSA)26Sortm1(HIF1A/luc)Kael | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, William G Kaelin | ||
| Common Name(s) | ODD-Luc; ROSA26 ODD-Luc; | ||
| Mutation Made By | William Kaelin, Dana Farber Cancer Institute | ||
| Strain of Origin | 129S6/SvEvTac | ||
| ES Cell Line Name | TC-1 | ||
| ES Cell Line Strain | 129S6/SvEvTac | ||
| Site of Expression | Under normal oxygen concentrations the (HIF1A) oxygen-dependent degradation domain(ODD)/luciferase fusion protein is degraded and shows little or no luciferase fluorescence. Under hypoxia, ubiquitination is attenuated, resulting in stabilization of the fusion protein and high levels of luciferase fluorescence in the hypoxic tissue(s). | ||
| Gene Symbol and Name | Gt(ROSA)26Sor, gene trap ROSA 26, Philippe Soriano | ||
| Chromosome | 6 | ||
| Gene Common Name(s) | AV258896; Gtrgeo26; Gtrosa26; R26; ROSA26; beta geo; expressed sequence AV258896; gene trap ROSA 26; gene trap ROSA b-geo 26; | ||
| Molecular Note | The human hypoxia-inducible factor 1 alpha sequence coding for amino acids 530-652, including the C-terminal portion of the oxygen-dependent degradation domain (ODD) was fused to the firefly luciferase (luc). The fusion protein was preceded by a loxP-flanked PGK-neo cassette and followed by a bovine polyadenylation sequence. The loxP-flanked neomycin was removed by crossing to a cre-expressing mouse line. In the resulting mice, hypoxia results in stabilization of the fusion protein and enhanced fluorescence detectable in hypoxic tissue. [MGI Ref ID J:118308] | ||
Control Information
| Control | ||
|---|---|---|
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
Genotyping Protocols
Gt(ROSA)26Sortm1(HIF1A/luc)Kael
Colony Maintenance
| Breeding & Husbandry | When maintaining a live colony, these mice may be bred as heterozygotes or homozygotes. |
|---|---|
| Diet Information | LabDiet® 5K52/5K67 |
Related Strains
Fluorescent Protein Strains
View Fluorescent Protein Strains (145 strains)
Additional Web Information
Congenic Nomenclature
Fluorescent Proteins/lacZ Systems
Animal Health Reports
Room Number AX11
Research Applications
This mouse can be used to support research in many areas including:
Cardiovascular Research
Ischemia studies
Internal/Organ Research
Heart Abnormalities
Lung Defects
Wound Healing
Research Tools
Cancer Research
Cardiovascular Research
Fluorescent Proteins
Genetics Research (Tissue/Cell Markers)
Internal/Organ Research
Metabolism Research
Toxicology Research
References
Selected Reference(s)
Safran M; Kim WY; O'Connell F; Flippin L; Gunzler V; Horner JW; Depinho RA; Kaelin WG Jr. 2006. Mouse model for noninvasive imaging of HIF prolyl hydroxylase activity: assessment of an oral agent that stimulates erythropoietin production. Proc Natl Acad Sci U S A 103(1):105-10. [PubMed: 16373502] [MGI Ref ID J:118308]
Price and Supply Information
| Strain Name: | FVB.129S6-Gt(ROSA)26Sortm1(HIF1A/luc)Kael/J |
| Stock Number: | 006206 |
Price Details
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Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
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| Supply Notes |
Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection. |
| Licensing | See General Terms and Conditions below for Licensing and Use Restrictions |
| Control Information | View Control Information in Strain Details. |
General Terms and Conditions
View JAX® Mice & Services Conditions of Use.
Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.
For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.
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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.Ordering and Purchasing Information
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