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| 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. | |||||||||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
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Description
Strain Information
Former Names FVB.129S6-Gt(ROSA)26Sortm1(HIF1A/luc)Kael/J (Changed: 20-FEB-09 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote (Female x Male) 11-MAR-08 Species laboratory mouse Generation N7+F7 (22-OCT-09) Donating Investigator William Kaelin, Dana Farber Cancer Institute 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.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 wild-type FVB mice (and selected against the Cre transgene) for 6 generations prior to arrival at The Jackson Laboratory.
Control Information
| Control | ||
|---|---|---|
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
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Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Gt(ROSA)26Sortm2(HIF1A/luc)Kael/Gt(ROSA)26Sor+
involves: 129S6/SvEvTac
- normal phenotype
- no abnormal phenotype detected (MGI Ref ID J:118308)
- fusion gene is expressed ubiquitously; with tissue hypoxia, luciferase expression is enhanced in those tissues
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
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Gt(ROSA)26Sortm2(HIF1A/luc)Kael | ||
|---|---|---|---|
| Allele Name | targeted mutation 2, William G Kaelin | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | Gt(ROSA)26Sortm1(HIF1A/luc)Kael; 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] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Gt(ROSA)26Sortm1(HIF1A/luc)Kael, Separated PCR
Gt(ROSA)26Sortm1(HIF1A/luc)Kael, Separated PCR
Helpful Links
Genotyping resources and troubleshooting
References
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]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice may be bred as heterozygotes or homozygotes. Mating System Homozygote x Homozygote (Female x Male) 11-MAR-08 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $160.40 Female or Male Homozygous for Gt(ROSA)26Sortm2(HIF1A/luc)Kael
Pairs /Price (US dollars $) Pair Genotype $320.80 Homozygous for Gt(ROSA)26Sortm2(HIF1A/luc)Kael x Homozygous for Gt(ROSA)26Sortm2(HIF1A/luc)Kael
Additional Supply Details
| Pricing for International shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $208.60 Female or Male Homozygous for Gt(ROSA)26Sortm2(HIF1A/luc)Kael
Pairs /Price (US dollars $) Pair Genotype $417.10 Homozygous for Gt(ROSA)26Sortm2(HIF1A/luc)Kael x Homozygous for Gt(ROSA)26Sortm2(HIF1A/luc)Kael
Additional Supply 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 approximately 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 two business days following order placement. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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