Strain Name:

STOCK Tg(Ins2-rtTA)2Efr/J

Stock Number:

008250

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Common Names: Ins-rtTA;     RIP7-rtTA;     RiprtTA;    
Ins-rtTA (or RIP7-rtTA) transgenic mice express the reverse tetracycline-controlled transactivator (rtTA) protein under the control of the rat insulin 2 (Ins2) promoter. When mated to a second transgenic strain carrying a gene under the regulatory control of a tetracycline-responsive promoter element (TRE or tetO), expression of the gene in pancreatic beta cells is induced with administration of the tetracycline analog, doxycycline (dox). This strain provides a Tet-On tool that allows the inducible expression of genes in pancreatic beta cells.

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

Type Mutant Stock; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
 
Donating Investigator Douglas A Melton,   Harvard University

Description
These mice express the reverse tetracycline-controlled transactivator (rtTA) protein under the control of the rat insulin 2 (Ins2) promoter. When mated to a second transgenic strain carrying a gene under the regulatory control of a tetracycline-responsive promoter element (tetO), expression of the gene may be regulated by the tetracycline analog, doxycycline (dox); in the presence of dox, transcription of the target gene is induced in pancreatic beta cells where rtTA is expressed. Induction of rtTA activity was not detected in other tissues. This strain provides a Tet-On tool that allows the inducible expression of genes in pancreatic beta cells. The Donating Investigator reports that homozygotes are viable and fertile.

Development
A transgenic construct containing the reverse tetracycline-controlled transactivator (rtTA) gene, 9.5kb 5' regulatory sequence and first intron of the rat insulin 2 gene (RIP7) and polyadenylation site sequence was injected into fertilized (C57BL/6 X CBA)F2 mouse eggs. Founder line 2 with 10 copies of the transgene was established and backcrossed to C57BL/6 for at least 3 generations. The mice were then maintained on the outbred ICR background. The mice were then crosssed to C57BL/6J once at The Jackson Laboratory.

Control Information

  Control
   None Available
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Tg(Ins2-rtTA)2Efr allele
008755   STOCK Tg(Ins2-rtTA)2Efr Tg(teto-DTA)1Gfi/J
View Strains carrying   Tg(Ins2-rtTA)2Efr     (1 strain)

Strains carrying other alleles of Ins2
005534   B10.Cg-H2d Tg(Ins2-HA)165Bri/ShrmJ
005500   B6.C-Tg(Ins2-GP)34-20Olds/MvhJ
005715   B6.Cg H2g7-Tg(Ins2-CD80)3B7Flv/LwnJ
004826   B6.Cg-Tg(Ins2-NP)25-3Olds/MhvJ
003573   B6.Cg-Tg(Ins2-cre)25Mgn/J
018960   B6N.Cg-Tg(Ins2-cre)25Mgn/J
005713   C.Cg-Tg(Ins2-CD80)3B7Flv/LwnJ
005533   C.Cg-Tg(Ins2-HA)165Bri/ShrmJ
004827   C.Cg-Tg(Ins2-NP)25-3Olds/MvhJ
005432   C57BL/6-Tg(Ins2-OVA)307Wehi/WehiJ
005433   C57BL/6-Tg(Ins2-OVA)59Wehi/WehiJ
005431   C57BL/6-Tg(Ins2-TFRC/OVA)296Wehi/WehiJ
005564   FVB(Cg)-Tg(Ins2-CALM1)26Ove Tg(Cryaa-TAg)1Ove/PneJ
008232   FVB/N-Tg(Ins2-IAPP)RHFSoel/J
005522   NOD-Tg(Ins2*Y16A)1Ell/GseJ
005523   NOD-Tg(Ins2*Y16A)3Ell/GseJ
003499   NOD-Tg(Ins2-Fasl)24Ach
004346   NOD.Cg-Prkdcscid Tg(Ins2-CD80)3B7Flv/DvsJ
004230   NOD.Cg-Prkdcscid Tg(Ins2-E3)1Dvs/DvsJ
003843   NOD.Cg-Prkdcscid Tg(Ins2-GAD2)1Lt/LtJ
003844   NOD.Cg-Prkdcscid Tg(Ins2-GAD2)2Lt/LtJ
007840   NOD.Cg-Prkdcscid Tg(Ins2-CD86)12B70Flv/FswJ
005524   NOD.Cg-Tg(Ins2*Y16A)1Ell Ins1tm1Jja Ins2tm1Jja/GseJ
005525   NOD.Cg-Tg(Ins2*Y16A)3Ell Ins1tm1Jja Ins2tm1Jja/GseJ
006254   NOD.Cg-Tg(Ins2-Ccl21b)2Cys/JbsJ
006154   NOD.Cg-Tg(Ins2-Cxcl13)1Cys/JbsJ
003869   NOD.Cg-Tg(Ins2-E3)1Dvs/DvsJ
005685   NOD.Cg-Tg(Ins2-HA)165Bri/ShrmJ
002380   NOD.Cg-Tg(Ins2-TAg)1Lt Prkdcscid/DvsJ
023972   NOD.Cg-Tg(Ins2-cre/ERT)1Dam/SbwJ
004602   NOD.Cg-Tg(Ins2-rtTA)2Doi/DoiJ
004937   NOD.Cg-Tg(Ins2-tTA)1Doi/DoiJ
005734   NOD/Lt-Tg(Ins2-rtTA)1Ach/AchJ
005870   NOD/ShiLt(Cg)-Tg(Ins2-GAD2)2Lt/J
006777   NOD/ShiLt-Tg(Ins2-Cd274)2Mdos/MdosJ
005733   NOD/ShiLt-Tg(Ins2-Fas*I246N)1Ach/AchJ
003074   NOD/ShiLt-Tg(Ins2-GAD2)1Lt/LtJ
002033   NOD/ShiLt-Tg(Ins2-TAg)1Lt/J
004986   NOD/ShiLt-Tg(Ins2-cre)3Lt/LtJ
003855   NOD/ShiLt-Tg(Ins2-cre)5Lt/LtJ
004987   NOD/ShiLt-Tg(Ins2-cre)6Lt/LtJ
004226   NOD/ShiLtDvs-Tg(Ins2-E3*309)5Dvs/DvsJ
004227   NOD/ShiLtDvs-Tg(Ins2-E3*704)2Dvs/DvsJ
004968   NOD/ShiLtDvs-Tg(Ins2-E3*734)3Dvs/DvsJ
004990   NOD/ShiLtDvs-Tg(Ins2-E3*734)4Dvs/DvsJ
005714   NOR.Cg-Tg(Ins2-CD80)3B7Flv/LwnJ
008122   STOCK Tg(Ins2-cre/ERT)1Dam/J
View Strains carrying other alleles of Ins2     (47 strains)

Strains carrying other alleles of rtTA
016567   129S.Cg-Tg(Hoxb7-rtTA*M2)2Cos/J
017983   B6.Cg-Col1a1tm9(tetO-Dnmt3b_i1)Jae Gt(ROSA)26Sortm1(rtTA*M2)Jae/J
014588   B6.Cg-Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm6(tetO-MSI2)Jae/J
014602   B6.Cg-Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm1(tetO-mCherry)Eggn/J
023749   B6.Cg-Gt(ROSA)26Sortm1(rtTA*M2)Jae Tg(tetO-Pou5f1,-Sox2,-Klf4,-Myc)1Srn/J
006965   B6.Cg-Gt(ROSA)26Sortm1(rtTA*M2)Jae/J
005670   B6.Cg-Gt(ROSA)26Sortm1(rtTA,EGFP)Nagy/J
016997   B6.Cg-Tg(Axin2-rtTA2S*M2)7Cos/J
012418   B6.Cg-Tg(CD68-rtTA2S*M2)3Mpil/Mmjax
014098   B6.Cg-Tg(GFAP-rtTA*M2)1Rmra/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
021025   B6;129-Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm1(tetO-cre)Haho/J
006911   B6;129-Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm2(tetO-Pou5f1)Jae/J
016836   B6;129S4-Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm7(tetO-HIST1H2BJ/GFP)Jae/J
012433   B6;C3-Tg(ACTA1-rtTA,tetO-cre)102Monk/J
021187   B6;FVB-Tg(Pbsn-rtTA*M2)42Xy/J
010574   B6;SJL-Tg(Gh1-rtTA)4-3Jek/J
007678   B6;SJL-Tg(KRT14-rtTA)208Jek/J
010576   B6;SJL-Tg(MMTV-rtTA)4-1Jek/J
010549   B6N.Cg-Tg(Prkcd-glc-1-rtTA)2And/J
016532   B6N.FVB(Cg)-Tg(CAG-rtTA3)4288Slowe/J
006245   C.Cg-Tg(SFTPC-rtTA)5Jaw/J
006242   C.Cg-Tg(Scgb1a1-rtTA)1Jaw/J
017955   C57BL/6-Tg(Gfap-rtTA,tetO-MAOB,-lacZ)1Jkan/J
008099   FVB-Tg(KRT14-rtTA)F42Efu/J
004127   FVB-Tg(Nes-rtTA)306Rvs/J
008326   FVB-Tg(Pomc-rtTA)1Rck/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
011004   STOCK Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm3(tetO-Pou5f1,-Sox2,-Klf4,-Myc)Jae/J
011011   STOCK Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm4(tetO-Pou5f1,-Sox2,-Klf4,-Myc)Jae/J
011013   STOCK Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm5(tetO-Pou5f1,-Klf4,-Myc)Jae/J
005572   STOCK Gt(ROSA)26Sortm1(rtTA,EGFP)Nagy/J
016116   STOCK Waptm2(rtTA)Kuw/J
003273   STOCK Tg(CMV-rtTA)4Bjd/J
018156   STOCK Tg(Drd1a-rtTA)ARgmk/J
019110   STOCK Tg(Hoxb7-rtTA*M2)RS40BCos/Mmjax
017519   STOCK Tg(KRT5-rtTA)T2D6Sgkd/J
016146   STOCK Tg(SFTPC-rtTA)2Jaw/J
016145   STOCK Tg(Scgb1a1-rtTA)2Jaw/J
005493   STOCK Tg(Tek-rtTA,TRE-lacZ)1425Tpr/J
View Strains carrying other alleles of rtTA     (47 strains)

Additional Web Information

Tet Expression Systems

Phenotype

Phenotype Information

View Research Applications

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

Research Tools
Tet Expression Systems
      tTA/rtTA Expressing Strains

Genes & Alleles

Gene & Allele Information provided by MGI

 
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 Expressionpancreatic 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]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(Ins2-rtTA)2Efr, Standard PCR
Tg(tTA), Melt Curve Analysis
Tg(tTA), QPCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

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

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]

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]

Tg(Ins2-rtTA)2Efr related

Balcazar 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]

Berkovich I; Efrat S. 2001. Inducible and Reversible beta-Cell Autoimmunity and Hyperplasia in Transgenic Mice Expressing a Conditional Oncogene. Diabetes 50(10):2260-7. [PubMed: 11574407]  [MGI Ref ID J:71705]

Cai Q; Brissova M; Reinert RB; Pan FC; Brahmachary P; Jeansson M; Shostak A; Radhika A; Poffenberger G; Quaggin SE; Jerome WG; Dumont DJ; Powers AC. 2012. Enhanced expression of VEGF-A in beta cells increases endothelial cell number but impairs islet morphogenesis and beta cell proliferation. Dev Biol 367(1):40-54. [PubMed: 22546694]  [MGI Ref ID J:185806]

De Leu N; Heremans Y; Coppens V; Van Gassen N; Cai Y; D'Hoker J; Magenheim J; Salpeter S; Swisa A; Khalaileh A; Arnold C; Gradwohl G; Van de Casteele M; Keshet E; Dor Y; Heimberg H. 2014. Short-term overexpression of VEGF-A in mouse beta cells indirectly stimulates their proliferation and protects against diabetes. Diabetologia 57(1):140-7. [PubMed: 24121626]  [MGI Ref ID J:206478]

Eldor R; Abel R; Sever D; Sadoun G; Peled A; Sionov R; Melloul D. 2013. Inhibition of nuclear factor-kappaB activation in pancreatic beta-cells has a protective effect on allogeneic pancreatic islet graft survival. PLoS One 8(2):e56924. [PubMed: 23437272]  [MGI Ref ID J:199335]

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]

Gupta S; McGrath B; Cavener DR. 2009. PERK regulates the proliferation and development of insulin-secreting beta-cell tumors in the endocrine pancreas of mice. PLoS One 4(11):e8008. [PubMed: 19956728]  [MGI Ref ID J:155377]

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]

Porat S; Weinberg-Corem N; Tornovsky-Babaey S; Schyr-Ben-Haroush R; Hija A; Stolovich-Rain M; Dadon D; Granot Z; Ben-Hur V; White P; Girard CA; Karni R; Kaestner KH; Ashcroft FM; Magnuson MA; Saada A; Grimsby J; Glaser B; Dor Y. 2011. Control of pancreatic beta cell regeneration by glucose metabolism. Cell Metab 13(4):440-9. [PubMed: 21459328]  [MGI Ref ID J:172243]

Pullen TJ; Sylow L; Sun G; Halestrap AP; Richter EA; Rutter GA. 2012. Overexpression of monocarboxylate transporter-1 (SLC16A1) in mouse pancreatic beta-cells leads to relative hyperinsulinism during exercise. Diabetes 61(7):1719-25. [PubMed: 22522610]  [MGI Ref ID J:192583]

Sodir NM; Swigart LB; Karnezis AN; Hanahan D; Evan GI; Soucek L. 2011. Endogenous Myc maintains the tumor microenvironment. Genes Dev 25(9):907-16. [PubMed: 21478273]  [MGI Ref ID J:171447]

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

Animal Health Reports

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

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice may be bred as hemizygotes or homozygotes.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2085.00
Animals Provided

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.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    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 11 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. IMPORTANT NOTE: 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2710.50
Animals Provided

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.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    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 11 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. IMPORTANT NOTE: 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   None Available
 
  Considerations for Choosing Controls
  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.
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