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| Targeted mutant mice have widespread expression of an optimized form of reverse tetracycline-controlled transactivator (rtTA-M2) protein. This R26-M2rtTA strain may be useful for doxycycline-inducible studies which utilize rtTA/tet-O (tet-on/TRE) models. | |||||||||||||||||||
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Description
Strain Information
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) 01-OCT-09 Species laboratory mouse Generation N10F1 (12-NOV-09)
Generation DefinitionsDonating Investigator Dr. Rudolf Jaenisch, Whitehead Institute (MIT) Description
Homozygotes are viable, fertile, normal in size and do not display any behavioral abnormalities. These targeted mutant mice have widespread expression of an optimized form of reverse tetracycline-controlled transactivator (rtTA-M2) protein. This R26-M2rtTA strain may be useful for doxycycline-inducible studies which utilize rtTA/tet-O (tet-on/TRE) models.Development
A targeting vector was designed to insert an optimized form of reverse tetracycline controlled transactivator (rtTA-M2) followed by a β-globin intron and polyA signal downstream of the Gt(ROSA)26Sor promoter. This construct was electroporated into (C57BL/6 x 129S4Sv/Jae)F1-derived V6.5 embryonic stem (ES) cells. In addition, these ES cells were retargeted to insert an frt-flanked PGK-Neo was into the 3' UTR of the Col1a1 locus. Correctly targeted ES cells were selected and the frt-flanked PGK-Neo in the 3' UTR of the Col1a1 locus was replaced by injecting both a "flip-in plasmid" containing a splice acceptor-double polyA sequence and the tetracycline responsive element (TRE or tetO) upstream of the mouse Oct4 (Pou5f1) cDNA sequence, as well as a Flpe-expressing plasmid to facilitate tetO-Oct4 recombination into the 3' UTR of the Col1a1 locus. The resulting ES cells (now targeted with rtTA-M2 in the Gt(ROSA)26Sor locus and tetO-Oct4 in the Col1a1 locus) were injected into B6D2F1 tetraploid blastocysts. Chimeric mice were bred together for many generations prior to arrival at The Jackson Laboratory (as Stock No. Stock No. 006911). Upon arrival, a subset of mice were backcrossed to C57BL/6J; selecting mice harboring the mutant Gt(ROSA)26Sor allele (not harboring the Col1a1 mutant locus) for at least 5 generations to generate this congenic strain (Stock No. 006965).
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying Gt(ROSA)26Sortm1(rtTA*M2)Jae allele
View Strains carrying Gt(ROSA)26Sortm1(rtTA*M2)Jae (7 strains)
Additional Web Information
Tet Expression Systems
Phenotype
Phenotype Information
This mouse can be used to support research in many areas including:
Neurobiology Research
Tet Expression System
tTA/rtTA Expressing Strains
Research Tools
Cancer Research
Tetop Tet System
Cardiovascular Research
Tetop Tet System
Genetics Research
Mutagenesis and Transgenesis
Mutagenesis and Transgenesis: Tetop Tet System
Neurobiology Research
Tetop Tet System
Reproductive Biology Research
Tetop Tet System
Tet Expression Systems
tTA/rtTA Expressing Strains
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Gt(ROSA)26Sortm1(rtTA*M2)Jae | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Rudolf Jaenisch | ||
| Allele Type | Targeted (knock-in) | ||
| Common Name(s) | Gt(ROSA)26Sortm1(M2rtTA)Jae; R26-M2rtTA; R26-rtTA; Rosa26-rtRA-nls; | ||
| Mutation Made By | Dr. Rudolf Jaenisch, Whitehead Institute (MIT) | ||
| Strain of Origin | (C57BL/6 x 129S4/SvJae)F1 | ||
| ES Cell Line Name | v6.5 | ||
| ES Cell Line Strain | (C57BL/6 x 129S4/SvJae)F1 | ||
| Site of Expression | Expresses an optimized rtTA protein (rtTA-M2). Inducible target gene expression is detected in liver, bone marrow, stomach, intestine, and skin, with lower levels in the heart, lungs, kidney, spleen, and thymus; no expression is detected in the brain and testes. | ||
| 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). | |||
| General Note | This mutation was originally created downstream of the Col1a1tm2(tetO-Pou5f1)Jae allele in mutant ES cell line KH2 but the two mutations have subsequently been bred apart. | ||
| Molecular Note | An optimized form of reverse tetracycline controlled transactivator (rtTA-M2) was inserted downstream of the Gt(ROSA)26Sor promoter. This mutant form of rtTA termed M2 has five amino acid substitutions in the tetR moiety of tTA: S12G, E19G, A56P, D148E and H179R. This mutated form of transactivatory protein has increased doxycycline sensitivity. Mice have widespread expression of the rtTA-M2 protein. [MGI Ref ID J:98920] | ||
| 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; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Gt(ROSA)26Sortm1sor STD, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Hochedlinger K; Yamada Y; Beard C; Jaenisch R. 2005. Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell 121(3):465-77. [PubMed: 15882627] [MGI Ref ID J:98920]
Additional References
Gt(ROSA)26Sortm1(rtTA*M2)Jae relatedAoki H; Hara A; Era T; Kunisada T; Yamada Y. 2012. Genetic ablation of Rest leads to in vitro-specific derepression of neuronal genes during neurogenesis. Development 139(4):667-77. [PubMed: 22241837] [MGI Ref ID J:181188]
Beard C; Hochedlinger K; Plath K; Wutz A; Jaenisch R. 2006. Efficient method to generate single-copy transgenic mice by site-specific integration in embryonic stem cells. Genesis 44(1):23-8. [PubMed: 16400644] [MGI Ref ID J:159351]
Brambrink T; Foreman R; Welstead GG; Lengner CJ; Wernig M; Suh H; Jaenisch R. 2008. Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells. Cell Stem Cell 2(2):151-9. [PubMed: 18371436] [MGI Ref ID J:149805]
Brennand K; Huangfu D; Melton D. 2007. All beta Cells Contribute Equally to Islet Growth and Maintenance. PLoS Biol 5(7):e163. [PubMed: 17535113] [MGI Ref ID J:124045]
Camargo FD; Gokhale S; Johnnidis JB; Fu D; Bell GW; Jaenisch R; Brummelkamp TR. 2007. YAP1 increases organ size and expands undifferentiated progenitor cells. Curr Biol 17(23):2054-60. [PubMed: 17980593] [MGI Ref ID J:141457]
Carey BW; Markoulaki S; Beard C; Hanna J; Jaenisch R. 2010. Single-gene transgenic mouse strains for reprogramming adult somatic cells. Nat Methods 7(1):56-9. [PubMed: 20010831] [MGI Ref ID J:157298]
Dickins RA; McJunkin K; Hernando E; Premsrirut PK; Krizhanovsky V; Burgess DJ; Kim SY; Cordon-Cardo C; Zender L; Hannon GJ; Lowe SW. 2007. Tissue-specific and reversible RNA interference in transgenic mice. Nat Genet 39(7):914-21. [PubMed: 17572676] [MGI Ref ID J:123006]
Foudi A; Hochedlinger K; Van Buren D; Schindler JW; Jaenisch R; Carey V; Hock H. 2009. Analysis of histone 2B-GFP retention reveals slowly cycling hematopoietic stem cells. Nat Biotechnol 27(1):84-90. [PubMed: 19060879] [MGI Ref ID J:172421]
Gros J; Hu JK; Vinegoni C; Feruglio PF; Weissleder R; Tabin CJ. 2010. WNT5A/JNK and FGF/MAPK pathways regulate the cellular events shaping the vertebrate limb bud. Curr Biol 20(22):1993-2002. [PubMed: 21055947] [MGI Ref ID J:166897]
Guo S; Bai H; Megyola CM; Halene S; Krause DS; Scadden DT; Lu J. 2012. Complex oncogene dependence in microRNA-125a-induced myeloproliferative neoplasms. Proc Natl Acad Sci U S A 109(41):16636-41. [PubMed: 23012470] [MGI Ref ID J:190324]
He S; Kim I; Lim MS; Morrison SJ. 2011. Sox17 expression confers self-renewal potential and fetal stem cell characteristics upon adult hematopoietic progenitors. Genes Dev 25(15):1613-27. [PubMed: 21828271] [MGI Ref ID J:174416]
Heinonen KM; Vanegas JR; Brochu S; Shan J; Vainio SJ; Perreault C. 2011. Wnt4 regulates thymic cellularity through the expansion of thymic epithelial cells and early thymic progenitors. Blood 118(19):5163-73. [PubMed: 21937690] [MGI Ref ID J:178890]
Hirata A; Utikal J; Yamashita S; Aoki H; Watanabe A; Yamamoto T; Okano H; Bardeesy N; Kunisada T; Ushijima T; Hara A; Jaenisch R; Hochedlinger K; Yamada Y. 2013. Dose-dependent roles for canonical Wnt signalling in de novo crypt formation and cell cycle properties of the colonic epithelium. Development 140(1):66-75. [PubMed: 23222438] [MGI Ref ID J:191050]
Holl D; Kuckenberg P; Woynecki T; Egert A; Becker A; Huss S; Stabenow D; Zimmer A; Knolle P; Tolba R; Fischer HP; Schorle H. 2011. Transgenic Overexpression of Tcfap2c/AP-2gamma Results in Liver Failure and Intestinal Dysplasia. PLoS One 6(7):e22034. [PubMed: 21779369] [MGI Ref ID J:174049]
Jaako P; Flygare J; Olsson K; Quere R; Ehinger M; Henson A; Ellis S; Schambach A; Baum C; Richter J; Larsson J; Bryder D; Karlsson S. 2011. Mice with ribosomal protein S19 deficiency develop bone marrow failure and symptoms like patients with Diamond-Blackfan anemia. Blood 118(23):6087-96. [PubMed: 21989989] [MGI Ref ID J:179085]
Jansson L; Larsson J. 2012. Normal hematopoietic stem cell function in mice with enforced expression of the Hippo signaling effector YAP1. PLoS One 7(2):e32013. [PubMed: 22363786] [MGI Ref ID J:185310]
Jarde T; Evans RJ; McQuillan KL; Parry L; Feng GJ; Alvares B; Clarke AR; Dale TC. 2013. In vivo and in vitro models for the therapeutic targeting of Wnt signaling using a Tet-ODeltaN89beta-catenin system. Oncogene 32(7):883-93. [PubMed: 22469981] [MGI Ref ID J:193365]
Kharas MG; Lengner CJ; Al-Shahrour F; Bullinger L; Ball B; Zaidi S; Morgan K; Tam W; Paktinat M; Okabe R; Gozo M; Einhorn W; Lane SW; Scholl C; Frohling S; Fleming M; Ebert BL; Gilliland DG; Jaenisch R; Daley GQ. 2010. Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia. Nat Med 16(8):903-8. [PubMed: 20616797] [MGI Ref ID J:163322]
Laplante M; Horvat S; Festuccia WT; Birsoy K; Prevorsek Z; Efeyan A; Sabatini DM. 2012. DEPTOR Cell-Autonomously Promotes Adipogenesis, and Its Expression Is Associated with Obesity. Cell Metab 16(2):202-12. [PubMed: 22883231] [MGI Ref ID J:187378]
Linhart HG; Lin H; Yamada Y; Moran E; Steine EJ; Gokhale S; Lo G; Cantu E; Ehrich M; He T; Meissner A; Jaenisch R. 2007. Dnmt3b promotes tumorigenesis in vivo by gene-specific de novo methylation and transcriptional silencing. Genes Dev 21(23):3110-22. [PubMed: 18056424] [MGI Ref ID J:127808]
Lopez ME; Klein AD; Dimbil UJ; Scott MP. 2011. Anatomically defined neuron-based rescue of neurodegenerative niemann-pick type C disorder. J Neurosci 31(12):4367-78. [PubMed: 21430138] [MGI Ref ID J:170312]
Lopez ME; Klein AD; Hong J; Dimbil UJ; Scott MP. 2012. Neuronal and epithelial cell rescue resolves chronic systemic inflammation in the lipid storage disorder Niemann-Pick C. Hum Mol Genet 21(13):2946-60. [PubMed: 22493001] [MGI Ref ID J:184610]
Magnusson M; Brun AC; Miyake N; Larsson J; Ehinger M; Bjornsson JM; Wutz A; Sigvardsson M; Karlsson S. 2007. HOXA10 is a critical regulator for hematopoietic stem cells and erythroid/megakaryocyte development. Blood 109(9):3687-96. [PubMed: 17234739] [MGI Ref ID J:145322]
Markoulaki S; Hanna J; Beard C; Carey BW; Cheng AW; Lengner CJ; Dausman JA; Fu D; Gao Q; Wu S; Cassady JP; Jaenisch R. 2009. Transgenic mice with defined combinations of drug-inducible reprogramming factors. Nat Biotechnol 27(2):169-71. [PubMed: 19151700] [MGI Ref ID J:158492]
McJunkin K; Mazurek A; Premsrirut PK; Zuber J; Dow LE; Simon J; Stillman B; Lowe SW. 2011. Reversible suppression of an essential gene in adult mice using transgenic RNA interference. Proc Natl Acad Sci U S A 108(17):7113-8. [PubMed: 21482754] [MGI Ref ID J:171348]
Paliwal P; Conboy IM. 2011. Inhibitors of tyrosine phosphatases and apoptosis reprogram lineage-marked differentiated muscle to myogenic progenitor cells. Chem Biol 18(9):1153-66. [PubMed: 21944754] [MGI Ref ID J:190199]
Petrelli A; Carvello M; Vergani A; Lee KM; Tezza S; Du M; Kleffel S; Chengwen L; Mfarrej BG; Hwu P; Secchi A; Leonard WJ; Young D; Sayegh MH; Markmann JF; Zajac AJ; Fiorina P. 2011. IL-21 is an antitolerogenic cytokine of the late-phase alloimmune response. Diabetes 60(12):3223-34. [PubMed: 22013017] [MGI Ref ID J:191409]
Premsrirut PK; Dow LE; Kim SY; Camiolo M; Malone CD; Miething C; Scuoppo C; Zuber J; Dickins RA; Kogan SC; Shroyer KR; Sordella R; Hannon GJ; Lowe SW. 2011. A rapid and scalable system for studying gene function in mice using conditional RNA interference. Cell 145(1):145-58. [PubMed: 21458673] [MGI Ref ID J:171191]
Quere R; Andradottir S; Brun AC; Zubarev RA; Karlsson G; Olsson K; Magnusson M; Cammenga J; Karlsson S. 2011. High levels of the adhesion molecule CD44 on leukemic cells generate acute myeloid leukemia relapse after withdrawal of the initial transforming event. Leukemia 25(3):515-26. [PubMed: 21116281] [MGI Ref ID J:170242]
Sehrawat S; Koenig PA; Kirak O; Schlieker C; Fankhauser M; Ploegh HL. 2013. A catalytically inactive mutant of the deubiquitylase YOD-1 enhances antigen cross-presentation. Blood 121(7):1145-56. [PubMed: 23243279] [MGI Ref ID J:194608]
Stadtfeld M; Maherali N; Borkent M; Hochedlinger K. 2010. A reprogrammable mouse strain from gene-targeted embryonic stem cells. Nat Methods 7(1):53-5. [PubMed: 20010832] [MGI Ref ID J:159350]
Tumaneng K; Schlegelmilch K; Russell RC; Yimlamai D; Basnet H; Mahadevan N; Fitamant J; Bardeesy N; Camargo FD; Guan KL. 2012. YAP mediates crosstalk between the Hippo and PI(3)K-TOR pathways by suppressing PTEN via miR-29. Nat Cell Biol 14(12):1322-9. [PubMed: 23143395] [MGI Ref ID J:195253]
Wan M; Gu H; Wang J; Huang H; Zhao J; Kaundal RK; Yu M; Kushwaha R; Chaiyachati BH; Deerhake E; Chi T. 2013. Inducible mouse models illuminate parameters influencing epigenetic inheritance. Development 140(4):843-52. [PubMed: 23325759] [MGI Ref ID J:194064]
Wan M; Kaundal R; Huang H; Zhao J; Yang X; Chaiyachati BH; Li S; Chi T. 2013. A general approach for controlling transcription and probing epigenetic mechanisms: application to the CD4 locus. J Immunol 190(2):737-47. [PubMed: 23293358] [MGI Ref ID J:191711]
Watanabe S; Hirai H; Asakura Y; Tastad C; Verma M; Keller C; Dutton JR; Asakura A. 2011. MyoD gene suppression by Oct4 is required for reprogramming in myoblasts to produce induced pluripotent stem cells. Stem Cells 29(3):505-16. [PubMed: 21425413] [MGI Ref ID J:175957]
Wesemann DR; Portuguese AJ; Magee JM; Gallagher MP; Zhou X; Panchakshari RA; Alt FW. 2012. Reprogramming IgH isotype-switched B cells to functional-grade induced pluripotent stem cells. Proc Natl Acad Sci U S A 109(34):13745-50. [PubMed: 22869756] [MGI Ref ID J:188595]
Yamada K; Ohno T; Aoki H; Semi K; Watanabe A; Moritake H; Shiozawa S; Kunisada T; Kobayashi Y; Toguchida J; Shimizu K; Hara A; Yamada Y. 2013. EWS/ATF1 expression induces sarcomas from neural crest-derived cells in mice. J Clin Invest :. [PubMed: 23281395] [MGI Ref ID J:194505]
Yamada Y; Aoki H; Kunisada T; Hara A. 2010. Rest promotes the early differentiation of mouse ESCs but is not required for their maintenance. Cell Stem Cell 6(1):10-5. [PubMed: 20085738] [MGI Ref ID J:157076]
Zhu H; Shah S; Shyh-Chang N; Shinoda G; Einhorn WS; Viswanathan SR; Takeuchi A; Grasemann C; Rinn JL; Lopez MF; Hirschhorn JN; Palmert MR; Daley GQ. 2010. Lin28a transgenic mice manifest size and puberty phenotypes identified in human genetic association studies. Nat Genet 42(7):626-30. [PubMed: 20512147] [MGI Ref ID J:166568]
Zhu H; Shyh-Chang N; Segre AV; Shinoda G; Shah SP; Einhorn WS; Takeuchi A; Engreitz JM; Hagan JP; Kharas MG; Urbach A; Thornton JE; Triboulet R; Gregory RI; Altshuler D; Daley GQ. 2011. The Lin28/let-7 Axis Regulates Glucose Metabolism. Cell 147(1):81-94. [PubMed: 21962509] [MGI Ref ID J:177113]
Zong Y; Huang J; Sankarasharma D; Morikawa T; Fukayama M; Epstein JI; Chada KK; Witte ON. 2012. Stromal epigenetic dysregulation is sufficient to initiate mouse prostate cancer via paracrine Wnt signaling. Proc Natl Acad Sci U S A 109(50):E3395-404. [PubMed: 23184966] [MGI Ref ID J:193135]
van Amerongen R; Fuerer C; Mizutani M; Nusse R. 2012. Wnt5a can both activate and repress Wnt/beta-catenin signaling during mouse embryonic development. Dev Biol 369(1):101-14. [PubMed: 22771246] [MGI Ref ID J:187621]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, homozygous mice may be bred together. Mating System Homozygote x Homozygote (Female x Male) 01-OCT-09 Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $177.00 Female or Male Homozygous for Gt(ROSA)26Sortm1(rtTA*M2)Jae
Price per Pair (US dollars $) Pair Genotype $354.00 Homozygous for Gt(ROSA)26Sortm1(rtTA*M2)Jae x Homozygous for Gt(ROSA)26Sortm1(rtTA*M2)Jae Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
| Pricing for International shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $230.10 Female or Male Homozygous for Gt(ROSA)26Sortm1(rtTA*M2)Jae
Price per Pair (US dollars $) Pair Genotype $460.20 Homozygous for Gt(ROSA)26Sortm1(rtTA*M2)Jae x Homozygous for Gt(ROSA)26Sortm1(rtTA*M2)Jae Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
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|
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Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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