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| Both ubiquitin/proteasome system reporter (UPS reporter) founder lines, UbG76V-GFP/1 (Stock No. 008111) and UbG76V-GFP/2 (Stock No. 008112), may be useful for monitoring the role of ubiquitin/proteasome-dependent proteolysis in diverse disorders, and for efficacy trials testing the effect of compounds on the ubiquitin/proteasome system (including the effect of proteasome inhibitors as novel anticancer drugs). | |||||||||||||||
- Description
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Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Strain Information
Former Names B6.Cg-Tg(ACTB-Ub*G76V/GFP)1Dant/J (Changed: 08-MAY-08 ) Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N3pN1 Donating Investigator Nico Dantuma, Karolinska Institutet Description
Hemizygous transgenic mice are viable and fertile; they contain a green fluorescent protein (GFP) fused to a constitutively active degradation signal (UbG76V). Transgenic transcripts are detected in all tissues examined; however the G76V substitution leads to its ubiquitination and proteasomal degradation, rather than expression of the GFP fluorescent protein. Following administration of proteasome inhibitors, UbG76V accumulates and GFP-derived fluorescence is readily apparent, evidence of an impaired ubiquitin/proteasome system. Both of the ubiquitin/proteasome system reporter founder lines, UbG76V-GFP/1 (Stock No. 008111) and UbG76V-GFP/2 (Stock No. 008112), may be useful for monitoring the role of ubiquitin/proteasome-dependent proteolysis in diverse disorders, and in efficacy trials for monitoring the effect of compounds on the ubiquitin/proteasome system (for example, in tests with proteasome inhibitors as novel anticancer drugs). While this strain and Stock No. 008112 have similar expression patterns, the donating investigator reports that this high expressing line (UbG76V-GFP/1; Stock No. 008111) has very low, but detectable, background fluorescence in the brain, spinal cord, and exocrine pancreatic tissue, prior to administration of proteasome inhibitors. Investigators are urged to consider which of these two founder lines is best suited for their research, because this reported fluorescence may hinder the detection of subtle changes in reporter levels in some tissues.Development
The UbG76V-GFP transgene was designed with a chicken beta-actin promoter (and cytomegalovirus (CMV) immediate early enhancer) upstream of a green fluorescent protein (GFP) fused to a mutant ubiquitin moiety (UbG76V), a constitutively active proteasome degradation signal. The transgene was microinjected into the pronucleus of fertilized (CBAxC57BL/6)F1 oocytes, and the transgenic offspring bred to C57BL/6N. Founder line 1 (UbG76V-GFP/1) mice, with high expression of the transgene, were backcrossed to C57BL/6N for approximately 30 generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred with C57BL/6NJ (Stock No. 005304) to establish the colony.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 005304 C57BL/6NJ | (approximate) | |
| Considerations for Choosing Controls | ||
Related Strains
Fluorescent Protein Strains
View Fluorescent Protein Strains (225 strains)
Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
assigned by genotype
Tg(CAG-Ub*G76V/GFP)1Dant/0
B6N.Cg-Tg(CAG-Ub*G76V/GFP)1Dant
- normal phenotype
- no abnormal phenotype detected (MGI Ref ID J:127085)
- hemizygous mice are viable and fertile
This mouse can be used to support research in many areas including:
GFP relatedCancer Research
Other
Cell Biology Research
Post-translational Processing
Protein Processing
degradation
Neurobiology Research
Fluorescent protein expression in neural tissue
Research Tools
Cancer Research
Cell Biology Research
Fluorescent Proteins
Toxicology Research
drug/compound testing
Research Tools
Fluorescent Proteins
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(CAG-Ub*G76V/GFP)1Dant | ||
|---|---|---|---|
| Allele Name | transgene insertion 1, Nico Dantuma | ||
| Allele Type | Transgenic (Reporter) | ||
| Common Name(s) | Tg(ACTB-Ub*G76V/GFP)1Dant; Tg(CAG-Ub*G76V/GFP)1Dant; UPS reporter; UbG76V-GFP/2; UbG76V-GFP/1; | ||
| Mutation Made By | Nico Dantuma, Karolinska Institutet | ||
| Strain of Origin | (CBA x C57BL/6)F1 | ||
| Site of Expression | Transgene transcripts are detected in all tissues examined; however the G76V substitution leads to degradation, of the GFP. Following administration of proteasome inhibitors, UbG76V accumulates and GFP-derived fluorescence is apparent. This strain is a high expressing line and has very low, but detectable, background fluorescence in the brain, spinal cord, and exocrine pancreatic tissue, prior to administration of proteasome inhibitors. | ||
| Expressed Gene | GFP, Green Fluorescent Protein, jellyfish | ||
| Green Fluorescent Protein (GFP), derived from the jellyfish Aequorea victoria, is a versatile reporter molecule which has found use in many biological applications. In some constructs the original molecule has been modified in order to enhance its fluorescence intensity (EGFP, enhanced GFP). When utilized in a transgenic construct, tissue expressing sufficient amounts of GFP will fluoresce when exposed to a 488 nm light source. | |||
| Promoter | ACTB, actin, beta, chicken | ||
| Molecular Note | The UbG76V-GFP transgene was designed with a chicken beta-actin promoter (and cytomegalovirus (CMV) immediate early enhancer) upstream of a green fluorescent protein (GFP) fused to a mutant ubiquitin moiety (UbG76V). Although transcripts of the UbG76V-GFP fusion gene are detected in all tissues examined, the G76V substitution prevents removal of the ubiquitin moiety leading to efficient ubiquitination and proteasomal degradation of the fusion protein (and thus no fluorescence) in these tissues. Line 1 with high expression was maintained by backcrosses to C57BL/6N mice. The high expressing line (UbG76V-GFP/1) has very low, but detectable, fluorescence expression in brain, spinal cord, and exocrine pancreatic tissue prior to administration of proteasome inhibitors. [MGI Ref ID J:127085] [MGI Ref ID J:127087] | ||
| Gene Symbol and Name | Tg(CAG-Ub*G76V/GFP)1Dant, transgene insertion 1, Nico Dantuma | ||
| Chromosome | UN | ||
| Gene Common Name(s) | Tg(ACTB-Ub*G76V/GFP)1Dant; UPS reporter; UbG76V-GFP/2; UbG76V-GFP/1; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(CAG-Ub*G76V/GFP)1Dant, Tg(CAG-Ub*G76V/GFP)2Dant, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
Bowman AB; Yoo SY; Dantuma NP; Zoghbi HY. 2005. Neuronal dysfunction in a polyglutamine disease model occurs in the absence of ubiquitin-proteasome system impairment and inversely correlates with the degree of nuclear inclusion formation. Hum Mol Genet 14(5):679-91. [PubMed: 15661755] [MGI Ref ID J:96393]
Lindsten K; Menendez-Benito V; Masucci MG; Dantuma NP. 2003. A transgenic mouse model of the ubiquitin/proteasome system. Nat Biotechnol 21(8):897-902. [PubMed: 12872133] [MGI Ref ID J:127085]
Additional References
Tg(CAG-Ub*G76V/GFP)1Dant relatedCheroni C; Marino M; Tortarolo M; Veglianese P; De Biasi S; Fontana E; Zuccarello LV; Maynard CJ; Dantuma NP; Bendotti C. 2009. Functional alterations of the ubiquitin-proteasome system in motor neurons of a mouse model of familial amyotrophic lateral sclerosis. Hum Mol Genet 18(1):82-96. [PubMed: 18826962] [MGI Ref ID J:142811]
Dantuma NP; Lindsten K; Glas R; Jellne M; Masucci MG. 2000. Short-lived green fluorescent proteins for quantifying ubiquitin/proteasome-dependent proteolysis in living cells. Nat Biotechnol 18(5):538-43. [PubMed: 10802622] [MGI Ref ID J:127087]
Lindsten K; de Vrij FM; Verhoef LG; Fischer DF; van Leeuwen FW; Hol EM; Masucci MG; Dantuma NP. 2002. Mutant ubiquitin found in neurodegenerative disorders is a ubiquitin fusion degradation substrate that blocks proteasomal degradation. J Cell Biol 157(3):417-27. [PubMed: 11980917] [MGI Ref ID J:127086]
Tokui K; Adachi H; Waza M; Katsuno M; Minamiyama M; Doi H; Tanaka K; Hamazaki J; Murata S; Tanaka F; Sobue G. 2009. 17-DMAG ameliorates polyglutamine-mediated motor neuron degeneration through well-preserved proteasome function in an SBMA model mouse. Hum Mol Genet 18(5):898-910. [PubMed: 19066230] [MGI Ref ID J:145004]
Health & husbandry
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, hemizygotes may be bred to wildtype siblings or to C57BL/6NJ (Stock No. 005304) inbred mice.
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $1900.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Additional Supply Details
| Pricing for International shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $2470.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Additional Supply Details
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Supply Details
| Standard Supply | Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 005304 C57BL/6NJ | (approximate) | |
| 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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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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