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| The Ins2-rtTA (or RIP7-rtTA) transgene expresses the reverse tetracycline-controlled transactivator (rtTA) protein under the control of the rat insulin 2 (Ins2) promoter. The tet-DTA (or tetO-DTA) (transgene expresses diphtheria toxin A (DTA) under the control of a tetracycline operator (tetO; also called tetracycline-responsive element (TRE) or tet-operator) and a cytomegalovirus minimal promoter. Mice harboring both of these transgenes has doxycycline-inducible expression of DTA in pancreatic beta cells; i.e. addition of the tetracycline analogue doxycycline (dox) results in ablation of pancreatic beta cells. | |||||||||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Mutant Stock; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System See Colony Maintenance Species laboratory mouse Generation F1 (14-JAN-09) Donating Investigator IMR Colony, The Jackson Laboratory Description
This strain was generated by breeding Stock No. 008168 and Stock No. 008250 together at The Jackson Laboratory. The resulting double transgenic colony was established as Stock No. 008755.The Ins2-rtTA (or RIP7-rtTA) transgene expresses the reverse tetracycline-controlled transactivator (rtTA) protein under the control of the rat insulin 2 (Ins2) promoter. The tet-DTA (or tetO-DTA) (transgene expresses diphtheria toxin A (DTA) under the control of a tetracycline operator (tetO; also called tetracycline-responsive element (TRE) or tet-operator) and a cytomegalovirus minimal promoter. Mice harboring both of these transgenes has doxycycline-inducible expression of DTA in pancreatic beta cells; i.e. addition of the tetracycline analogue doxycycline (dox) results in ablation of pancreatic beta cells.
Development
This strain was generated by breeding Stock No. 008168 and Stock No. 008250 together at The Jackson Laboratory. The resulting double transgenic colony was established (as Stock No. 008755). This strain was subsequently maintained by breeding mice carrying for both the RIP7-rtTA transgene and tet-DTA transgene together. The genetic background is a mix of C57BL/6, CBA, and outbred ICR.
Control Information
| Control | ||
|---|---|---|
| None Available | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying Tg(Ins2-rtTA)2Efr allele
008250 STOCK Tg(Ins2-rtTA)2Efr/J View Strains carrying Tg(Ins2-rtTA)2Efr (1 strain)
008468 B6.Cg-Tg(tetO-DTA)1Gfi/J 008168 STOCK Tg(tetO-DTA)1Gfi/J
008617 B6(A)-Tg(OPN1LW-DT)1Mame/J 006576 B6.FVB-Tg(GNAT2-Dta)98Wwk/J 002384 FVB/N-Tg(UcpDta)1Kz/J
006965 B6.Cg-Gt(ROSA)26Sortm1(rtTA*M2)Jae/J 005670 B6.Cg-Gt(ROSA)26Sortm1(rtTA,EGFP)Nagy/J 007176 B6.Cg-Tg(Pax8-rtTA2S*M2)1Koes/J 006235 B6.Cg-Tg(SFTPC-rtTA)5Jaw/J 006232 B6.Cg-Tg(Scgb1a1-rtTA)1Jaw/J 006911 B6;129-Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm2(tetO-Pou5f1)Jae/J 007678 B6;SJL-Tg(KRT14-rtTA)208Jek/J 010576 B6;SJL-Tg(MMTV-rtTA)4-1Jek/J 006245 C.Cg-Tg(SFTPC-rtTA)5Jaw/J 006242 C.Cg-Tg(Scgb1a1-rtTA)1Jaw/J 008099 FVB-Tg(KRT14-rtTA)F42Efu/J 004127 FVB-Tg(Nes-rtTA)306Rvs/J 006225 FVB.Cg-Tg(SFTPC-rtTA)5Jaw/J 006222 FVB.Cg-Tg(Scgb1a1-rtTA)1Jaw/J 008202 FVB/N-Tg(NPHS2-rtTA2*M2)1Jbk/J 006875 FVB/N-Tg(Tagln-rtTA)E1Jwst/J 004602 NOD.Cg-Tg(Ins2-rtTA)2Doi/DoiJ 005734 NOD/Lt-Tg(Ins2-rtTA)1Ach/AchJ 005572 STOCK Gt(ROSA)26Sortm1(rtTA,EGFP)Nagy/J 005493 STOCK Tg(Tek-rtTA,TRE-lacZ)1425Tpr/J 003273 STOCK Tg(rtTAhCMV)4Bjd/J
Additional Web Information
Tet Expression Systems
Phenotype
Phenotype Information
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(Ins2-rtTA)2Efr/0 Tg(tetO-DTA)1Gfi/0
involves: C57BL/6 * CBA
- endocrine/exocrine gland phenotype
- *normal* endocrine/exocrine gland phenotype (MGI Ref ID J:127412)
- average size of regenerating beta cells is same as original cells
- abnormal pancreas morphology (MGI Ref ID J:127412)
- pancreatic insulin content is reduced by ~85%; after doxycycline withdrawal, pancreatic insulin level return to near control levels
- abnormal pancreatic beta cell morphology (MGI Ref ID J:127412)
- frequency of insulin-positive, glucagons-positive beta cells increases from 1:5500 in controls to 1:1000 beta cells in diabetic transgenic mice
- permitting doxycycline-treated mice to recover in presence of immunosupressants Sirolimus and Tacrolimus (SirTac) significantly reduces beta cell proliferation and beta cell mass does not increase as it does in absence of immunosupressants; blood glucose levels in treated mice fail to normalize as they do in controls treated with SirTac
- decreased pancreatic beta cell number (MGI Ref ID J:127412)
- 70-80% of beta cells are lost in doxycycline-treated 5-week old double-transgenic mice relative to controls
- similar results are obtained when beta cells are ablated between birth and five weeks of age; beta cell mass normalizes within ~15 weeks of doxycycline withdrawal
- increased pancreatic beta cell number (MGI Ref ID J:127412)
- rate of beta cell apoptosis in recovering mice is not different from controls, but beta cell proliferation is increased 2-3-fold within 48 hours of onset of beta cell ablation; this increased proliferation rate is maintained for several weeks
- disorganized pancreatic islets (MGI Ref ID J:127412)
- treatment of four-week old mice with doxycycline for 1 week results in severely disrupted islet architecture with non-beta cells at the core of shriveled islets rather than beta cells
- after withdrawal of doxycycline, normalization of islet architecture occurs in ~90% of islets
- digestive/alimentary phenotype
- abnormal pancreas morphology (MGI Ref ID J:127412)
- pancreatic insulin content is reduced by ~85%; after doxycycline withdrawal, pancreatic insulin level return to near control levels
- abnormal pancreatic beta cell morphology (MGI Ref ID J:127412)
- frequency of insulin-positive, glucagons-positive beta cells increases from 1:5500 in controls to 1:1000 beta cells in diabetic transgenic mice
- permitting doxycycline-treated mice to recover in presence of immunosupressants Sirolimus and Tacrolimus (SirTac) significantly reduces beta cell proliferation and beta cell mass does not increase as it does in absence of immunosupressants; blood glucose levels in treated mice fail to normalize as they do in controls treated with SirTac
- decreased pancreatic beta cell number (MGI Ref ID J:127412)
- 70-80% of beta cells are lost in doxycycline-treated 5-week old double-transgenic mice relative to controls
- similar results are obtained when beta cells are ablated between birth and five weeks of age; beta cell mass normalizes within ~15 weeks of doxycycline withdrawal
- increased pancreatic beta cell number (MGI Ref ID J:127412)
- rate of beta cell apoptosis in recovering mice is not different from controls, but beta cell proliferation is increased 2-3-fold within 48 hours of onset of beta cell ablation; this increased proliferation rate is maintained for several weeks
- disorganized pancreatic islets (MGI Ref ID J:127412)
- treatment of four-week old mice with doxycycline for 1 week results in severely disrupted islet architecture with non-beta cells at the core of shriveled islets rather than beta cells
- after withdrawal of doxycycline, normalization of islet architecture occurs in ~90% of islets
- homeostasis/metabolism phenotype
- *normal* homeostasis/metabolism phenotype (MGI Ref ID J:127412)
- peripheral insulin sensitivity after beta cell regeneration is similar to controls after doxycycline withdrawal, beta cell mass in transgenic mice increases to levels comparable to wild-type
- improved glucose tolerance (MGI Ref ID J:127412)
- after more than 8 months without doxycycline, glucose tolerance starts to recover
- similar results are obtained when beta cells are ablated between birth and five weeks of age; beta cell mass normalizes within ~15 weeks of doxycycline withdrawal
- mice that showed severe, chronic or adult-onset (starting at 4 months) hyperglycemia spontaneously normalized blood glucose levels and beta-cell mass after doxycycline withdrawal
- increased circulating glucose level (MGI Ref ID J:127412)
- blood glucose levels of treated mice are elevated to 300-600 mg/dl making the mice overtly diabetic; after withdrawal of doxycycline, blood glucose levels return to normal level
- mice that showed severe, chronic or adult-onset (starting at 4 months) hyperglycemia spontaneously normalized blood glucose levels and beta-cell mass after doxycycline withdrawal
- hyperglycemia (MGI Ref ID J:127412)
- blood glucose levels are elevated to 300-600 mg/dl; after doxycycline withdrawal, remission of hyperglycemia occurs such that fed and fasting glucose levels normalize
- mice that showed severe, chronic or adult-onset (starting at 4 months) hyperglycemia spontaneously normalized blood glucose levels and beta-cell mass after doxycycline withdrawal
- cellular phenotype
- increased apoptosis (MGI Ref ID J:127412)
- widespread pancreatic beta cell apoptosis is seen within 48 hours of doxycycline treatment of double-transgenic mice, but no apoptosis is observed in single transgenic littermates
This mouse can be used to support research in many areas including:
Diabetes and Obesity Research
Type 1 Diabetes (IDDM)
Endocrine Deficiency Research
Pancreas Defects
Immunology and Inflammation Research
Autoimmunity
Type 1 Diabetes
Metabolism Research
Enzyme Deficiency
exocrine pancreatic insufficiency
Neurobiology Research
Tet Expression System
tTA/rtTA Expressing Strains
tTA/rtTA Responsive Strains
Research Tools
Cancer Research
Tetop Tet System
Cardiovascular Research
Tetop Tet System
Diabetes and Obesity Research
Genetics Research
Mutagenesis and Transgenesis: Tetop Tet System
Tissue/Cell Markers: pancreatic beta cells
Neurobiology Research
Tetop Tet System
Tet Expression Systems
tTA/rtTA Expressing Strains
tTA/rtTA Responsive Strains
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(Ins2-rtTA)2Efr | ||
|---|---|---|---|
| Allele Name | transgene insertion 2, Shimon Efrat | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | Ins-rtTA; RIP7-rtTA; RiprtTA; | ||
| Strain of Origin | (C57BL/6 x CBA)F2 | ||
| Site of Expression | pancreatic beta cells | ||
| Expressed Gene | rtTA, reverse tetracycline-controlled transactivator, E. coli | ||
| The tetracycline repressor gene (Tetr), arose from chemically mutated Escherichia coli genome which was screened for tetracycline dependence (Gossen and Bujard, 1992). One mutant with a four amino acid residue change (rTetR) exhibited dependence on tetracycline for induction of the targeted gene and was used in the rtTA construct (Gossen et al, 1995). rTetr was fused at the C-terminus with the viral co-activator, virion protein 16 of the herpes simplex virus (VP-16). | |||
| Promoter | Ins2, insulin 2, rat | ||
| Molecular Note | A transgenic construct containing 9.5kb 5' regulatory sequence and first intron of the rat insulin 2 gene (RIP7) controlling the reverse tetracycline transactivator (rtTA), as well as the polyadenylation site sequence of the RIP7 gene was injected into fertilized (C57BL/6 X CBA)F2 mouse eggs. Founder line 2 with 10 copies of the transgene was established. When mice are crossed to transgenic mice carrying reporter genes, transgene expression is detected only in pancreatic islet beta cells. [MGI Ref ID J:130049] | ||
| Allele Symbol | Tg(tetO-DTA)1Gfi | ||
| Allele Name | transgene insertion 1, Glenn I Fishman | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | tet-DTA; tetODTA/+; | ||
| Strain of Origin | (C57BL/6 x CBA)F2 | ||
| Expressed Gene | Dta, Diphtheria toxin A chain, | ||
| Brown fat specific expression of the A-chain of diptheria toxin (DTA) resulting in ablation of brown fat. | |||
| Promoter | tetO, tet operator, | ||
| Molecular Note | A transgenic construct was created, containing diphtheria toxin A sequence (DTA) under the control of heptamerized tetracycline operator, tetO sequences fused to a cytomegalovirus minimal promoter. [MGI Ref ID J:128617] | ||
Genotyping
Genotyping Information
This strain will not have a genotyping protocol or one is not currently available.
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
Lee P; Morley G; Huang Q; Fischer A; Seiler S; Horner JW; Factor S; Vaidya D; Jalife J; Fishman GI. 1998. Conditional lineage ablation to model human diseases. Proc Natl Acad Sci U S A 95(19):11371-6. [PubMed: 9736743] [MGI Ref ID J:128617]
Milo-Landesman D; Surana M; Berkovich I; Compagni A; Christofori G; Fleischer N; Efrat S. 2001. Correction of hyperglycemia in diabetic mice transplanted with reversibly immortalized pancreatic beta cells controlled by the tet-on regulatory system. Cell Transplant 10(7):645-50. [PubMed: 11714200] [MGI Ref ID J:130049]
Additional References
Tg(Ins2-rtTA)2Efr relatedTg(tetO-DTA)1Gfi relatedBalcazar N; Sathyamurthy A; Elghazi L; Gould A; Weiss A; Shiojima I; Walsh K; Bernal-Mizrachi E. 2009. mTORC1 activation regulates beta-cell mass and proliferation by modulation of cyclin D2 synthesis and stability. J Biol Chem 284(12):7832-42. [PubMed: 19144649] [MGI Ref ID J:148614]
Eldor R; Yeffet A; Baum K; Doviner V; Amar D; Ben-Neriah Y; Christofori G; Peled A; Carel JC; Boitard C; Klein T; Serup P; Eizirik DL; Melloul D. 2006. Conditional and specific NF-kappaB blockade protects pancreatic beta cells from diabetogenic agents. Proc Natl Acad Sci U S A 103(13):5072-7. [PubMed: 16551748] [MGI Ref ID J:107655]
Jaggi F; Cabrita MA; Perl AK; Christofori G. 2008. Modulation of endocrine pancreas development but not beta-cell carcinogenesis by Sprouty4. Mol Cancer Res 6(3):468-82. [PubMed: 18337453] [MGI Ref ID J:138091]
Nir T; Melton DA; Dor Y. 2007. Recovery from diabetes in mice by beta cell regeneration. J Clin Invest 117(9):2553-61. [PubMed: 17786244] [MGI Ref ID J:127412]
Nir T; Melton DA; Dor Y. 2007. Recovery from diabetes in mice by beta cell regeneration. J Clin Invest 117(9):2553-61. [PubMed: 17786244] [MGI Ref ID J:127412]
Stanger BZ; Tanaka AJ; Melton DA. 2007. Organ size is limited by the number of embryonic progenitor cells in the pancreas but not the liver. Nature 445(7130):886-91. [PubMed: 17259975] [MGI Ref ID J:118596]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry This strain was generated by breeding Stock No. 008168 and Stock No. 008250 together at The Jackson Laboratory. The resulting double transgenic colony was established (as Stock No. 008755). This strain was subsequently maintained by breeding mice carrying both the RIP7-rtTA transgene and tet-DTA transgene together. The genetic background is a mix of C57BL/6, CBA, and outbred ICR. Mating System See above Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
This strain is currently Under Development for Production.
To register your interest in this strain go to the Strain Interest Form.
Estimated Available for Sale Date: 23-NOV-09
Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.
View All Strains Under Development and On Hold
Supply Details
| Standard Supply | Under Development for Distribution Colony |
|---|---|
| Supply Notes |
|
Control Information
| Control | ||
|---|---|---|
| None Available | ||
| 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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