JAX Mouse Strain Datasheet - 008112

B6.Cg-Tg(CAG-Ub*G76V/GFP)2Dant/J

Stock No:: 008112

Cryo Recovery

Overview

Both ubiquitin/proteasome system reporter (UPS reporter) founder lines, Ub^G76V-GFP/1 (Stock No. 008111) and Ub^G76V-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).

Donating Investigator

Nico Dantuma, Karolinska Institutet

Genetic overview

Genetic Background	Generation

Tg(CAG-Ub*G76V/GFP)2Dant

Allele Type
Transgenic (Reporter)

View Genetics

Research Applications

Cancer Research
Cell Biology Research
Neurobiology Research
Research Tools

View All Research Applications

Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

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Details

Detailed Description

Hemizygous transgenic mice are viable and fertile; they contain the green fluorescent protein (GFP) fused to a constitutively active degradation signal (Ub^G76V). Transgenic transcripts are detected in all tissues examined; however no GFP protein expression is detected due to the G76V substitution which leads to its ubiquitination and proteasomal degradation. Following administration of proteasome inhibitors, Ub^G76V accumulates and GFP-derived fluorescence is readily apparent, evidence of an impaired ubiquitin/proteasome system. This strain and Ub^G76V-GFP/1 (Stock No. 008111) have similar expression patterns, but this line (Ub^G76V-GFP/2) shows lower transgene expression and is not reported to display background fluorescence. These strains may be useful for monitoring 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).

Development

The Ub^G76V-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 (Ub^G76V), a constitutively active proteasome degradation signal. The transgene was microinjected into the pronucleus of fertilized (CBAxC57BL/6)F1 oocytes, and the transgenic offspring e bred to C57BL/6N. Founder line 2 (Ub^G76V-GFP/2) mice, with lower expression of the transgene than line 1, 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.

Expression Data

Expressed Gene	GFP, Green Fluorescent Protein,
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, Ub^G76V accumulates and GFP-derived fluorescence is apparent. This line shows lower transgene expression and is not reported to display background fluorescence.

Control Suggestions

Noncarrier
005304 C57BL/6NJ

Additional Information

Considerations for Choosing Controls

Selected References

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: 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: J:127085

View All References

Genetics

Tg(CAG-Ub*G76V/GFP)2Dant

Allele Symbol: Tg(CAG-Ub*G76V/GFP)2Dant

Allele Name	transgene insertion 2, Nico Dantuma
Allele Type	Transgenic (Reporter)
Allele Synonym(s)	Tg(ACTB-UbG76V/GFP)2Dant; Tg(CAG-UbG76V/GFP)2Dant; UPS reporter; Ub^G76V-GFP/2; UbG76V-GFP/2
Gene Symbol and Name	Tg(CAG-Ub*G76V/GFP)2Dant, transgene insertion 2, Nico Dantuma
Gene Synonym(s)	Tg(ACTB-UbG76V/GFP)2Dant; Tg(ACTB-UbG76V/GFP)2Dant; UPS reporter; Ub^G76V-GFP/2; UbG76V-GFP/2
Promoter	ACTB, actin, beta, chicken
Expressed Gene	GFP, Green Fluorescent Protein,
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, Ub^G76V accumulates and GFP-derived fluorescence is apparent. This line shows lower transgene expression and is not reported to display background fluorescence.
Strain of Origin	(CBA x C57BL/6)F1
Chromosome	UN
Molecular Note	The Ub^G76V-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). This transgene was microinjected into the pronucleus of fertilized (CBA x C57BL/6)F1 oocytes. Although transcripts of the Ub^G76V-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 2 with low expression was maintained by backcross to C57BL/6N mice.
Mutations Made By	Nico Dantuma, Karolinska Institutet

Disease/Phenotype

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Cancer 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

Genotype: GFP related

Research Tools
- Fluorescent Proteins

Mammalian Phenotype Terms by Genotype

Genotype: Tg(CAG-UbG76V/GFP)2Dant/0
B6N.Cg-Tg(CAG-UbG76V/GFP)2Dant

normal phenotype

no abnormal phenotype detected
- hemizygous mice are viable and fertile

References

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: 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: J:127085

Additional - Tg(CAG-Ub*G76V/GFP)2Dant related

Berthet A; Bezard E; Porras G; Fasano S; Barroso-Chinea P; Dehay B; Martinez A; Thiolat ML; Nosten-Bertrand M; Giros B; Baufreton J; Li Q; Bloch B; Martin-Negrier ML. 2012. L-DOPA Impairs Proteasome Activity in Parkinsonism through D1 Dopamine Receptor. J Neurosci 32(2):681-91. PubMed: 22238104 MGI: J:179902
Cheroni 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: 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: 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: J:127086
Lobanova ES; Finkelstein S; Skiba NP; Arshavsky VY. 2013. Proteasome overload is a common stress factor in multiple forms of inherited retinal degeneration. Proc Natl Acad Sci U S A 110(24):9986-91. PubMed: 23716657 MGI: J:197400
Mammucari C; Milan G; Romanello V; Masiero E; Rudolf R; Del Piccolo P; Burden SJ; Di Lisi R; Sandri C; Zhao J; Goldberg AL; Schiaffino S; Sandri M. 2007. FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab 6(6):458-71. PubMed: 18054315 MGI: J:130442
Myeku N; Clelland CL; Emrani S; Kukushkin NV; Yu WH; Goldberg AL; Duff KE. 2016. Tau-driven 26S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling. Nat Med 22(1):46-53. PubMed: 26692334 MGI: J:233168
Quaglio E; Restelli E; Garofoli A; Dossena S; De Luigi A; Tagliavacca L; Imperiale D; Migheli A; Salmona M; Sitia R; Forloni G; Chiesa R. 2011. Expression of Mutant or Cytosolic PrP in Transgenic Mice and Cells Is Not Associated with Endoplasmic Reticulum Stress or Proteasome Dysfunction. PLoS One 6(4):e19339. PubMed: 21559407 MGI: J:172342

Pricing & Availability

Cryo Recovery

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Price

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Cryorecovery - Pricing

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	Please inquire about possible genotypes.

Progeny testing is not required

The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks.

The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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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.

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Licensing Information

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Tg(CAG-Ub*G76V/GFP)2Dant

Allele Symbol: Tg(CAG-Ub*G76V/GFP)2Dant

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Genotype: GFP related

Mammalian Phenotype Terms by Genotype

Genotype: Tg(CAG-Ub*G76V/GFP)2Dant/0B6N.Cg-Tg(CAG-Ub*G76V/GFP)2Dant

normal phenotype

References

Additional - Tg(CAG-Ub*G76V/GFP)2Dant related

Genotyping Protocols

Breeding Considerations

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Progeny testing is not required

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Genotype: Tg(CAG-UbG76V/GFP)2Dant/0
B6N.Cg-Tg(CAG-UbG76V/GFP)2Dant