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| These TRE-MYC (TetO-c-Myc or Teto-MYC) hemizygous transgenic mice carry the human myelocytomatosis oncogene, MYC, regulated by a tetracycline operator (tetO). These mice may be useful for studying tumor development and regression. | |||||||||||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
Strain Information
Type Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Donating Investigator J Michael Bishop, UCSF School of Medicine Description
Expression of MYC in these transgenic mice is regulated by a tetracycline operator (tetO). MYC is a transcription factor involved in cellular proliferation and differentiation, and is often upregulated in tumors, leukemias and lymphomas. Hemizygous mice are viable and fertile, homozygotes do not survive. When mated to a mutant strain expressing tetracycline-controlled transactivator protein (tTA), expression of MYC protein may be regulated with tetracycline or its analog doxycycline (dox) in the double mutant offspring.When bred to B6.Cg-Tg(Cebpb-tTA)5Bjd/J mice (as Stock No. 003563) expressing tTA in liver, withdrawal of dox from double transgenic mice develop invasive metastatic liver tumors, and all mice die within 2 weeks onset. When doxycycline treatment is re-administered, rapid and sustained tumor regression is evident.
When bred to B6.Cg-Tg(Pax8-rtTA2S*M2)1Koes/J (see Stock No. 007176) expressing rtTA in renal tubular epithelial cells, induction of doxycycline causes polycystic kidneys, kidney failure and renal adenomas.
Development
A transgenic vector was generated encoding the human myelocytomatosis viral oncogene cDNA (MYC) under control of a tetO promoter. The construct was microinjected into FVB/NJ fertilized oocytes, and mice from founder line 36a were bred to FVB/NJ mice for at least 10 generations to establish a colony. Upon arrival at The Jackson Laboratory Repository, mice were bred to FVB/NJ mice (as Stock No. 001800) for at least one generation.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | (approximate) | |
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of MYC
002712 FVB/N-Tg(PF4MER)6Kra/J View Strains carrying other alleles of MYC (1 strain)
Phenotype
Phenotype Information
- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.
Colorectal Cancer; CRC
Hepatocellular Carcinoma
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested. Burkitt Lymphoma; BL (MYC)
assigned by genotype
The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.Tg(Pax8-rtTA2S*M2)1Koes/0 Tg(tetO-MYC)36aBop/0
involves: C57BL/6 * DBA * FVB/N
- renal/urinary system phenotype
- kidney cysts
- following induction with doxycycline, mice develop glomerular cysts (MGI Ref ID J:140925)
- polycystic kidney
- following induction with doxycycline, mice develop multiple renal cysts in all renal tubular compartments (MGI Ref ID J:140925)
- kidney failure
- 3 to 4 months following induction with doxycycline (MGI Ref ID J:140925)
- tumorigenesis
- increased adenoma incidence
- following induction with doxycycline, mice develop renal adenomas (MGI Ref ID J:140925)
- increased renal carcinoma incidence
- following induction with doxycycline (MGI Ref ID J:140925)
Tg(tetO-MYC)36aBop/0 Tg(Cebpb-tTA)5Bjd/0
involves: FVB/N * NMRI
- mortality/aging
- premature death
- following withdrawal of doxycycline, all mice succumb to liver tumors within 2 weeks (MGI Ref ID J:93899)
- median survival of mutants is 31 weeks following doxycycline withdrawal to induce MYC expression (MGI Ref ID J:172430)
- median survival of mutants with tumors is 27 weeks following doxycycline withdrawal to induce MYC expression (MGI Ref ID J:172430)
- tumorigenesis
- decreased tumor growth/size
- doxycycline-treated mice infected with an adeno-associated virus-expressing Mir122 exhibit suppression of tumorigenesis tumor cell proliferation compared with control mice (MGI Ref ID J:190067)
- increased liver tumor incidence (MGI Ref ID J:172430)
- following withdrawal of doxycycline, mice develop tumors with a latency of 12 weeks and all mice succumb to liver tumors within 2 weeks (MGI Ref ID J:93899)
- liver tumors that develop in mice after doxycycline withdrawal are invasive and metastasis into the thoracic cavity and lung parenchyma (MGI Ref ID J:93899)
- however, re-establishment of doxycycline-treatment produces rapid and sustained tumor regression (MGI Ref ID J:93899)
- repeated withdrawal and treatment with doxycyclineinduces and represses, respectively, tumor formation (MGI Ref ID J:93899)
- hepatoblastoma
- liver tumors that develop in mice after doxycycline withdrawal resemble hepatocellular carcinomas and/or hepatoblastomas (MGI Ref ID J:93899)
- hepatocellular carcinoma
- liver tumors that develop in mice after doxycycline withdrawal resemble hepatocellular carcinomas and/or hepatoblastomas (MGI Ref ID J:93899)
- tumors that form in mice after doxycycline withdrawal are composed of hepatocellular neoplasms characterized by sheets of cells with occasional mitotic figure, slightly pleomorphic nuclei, and prominent nucleoli (MGI Ref ID J:172430)
- tumors show a range of differentiation between well- and moderately-differentiated hepatocellular carcinoma (MGI Ref ID J:172430)
- in doxycycline-treated mice (MGI Ref ID J:190067)
- however, treatment with adeno-associated virus-expressing Mir122 suppresses tumorigenesis (MGI Ref ID J:190067)
This mouse can be used to support research in many areas including:
Cancer Research
Genes Regulating Growth and Proliferation
Increased Tumor Incidence
Oncogenes
Other
tumor metastasis
Research Tools
Cancer Research
Tetop Tet System
Genetics Research
Mutagenesis and Transgenesis: Tetop Tet System
Tet Expression Systems
tTA/rtTA Responsive Strains
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(tetO-MYC)36aBop | ||
|---|---|---|---|
| Allele Name | transgene insertion 36a, J Michael Bishop | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | TRE-MYC; TetO-c-Myc; Teto-MYC; Tg(tetO-MYC)36Bop; | ||
| Mutation Made By | J Michael Bishop, UCSF School of Medicine | ||
| Strain of Origin | FVB/N | ||
| Expressed Gene | MYC, v-myc myelocytomatosis viral oncogene homolog (avian), human | ||
| Promoter | tetO, tet operator, | ||
| Molecular Note | This transgene contains a human v-myc avian myelocytomatosis viral oncogene homolog cDNA and regulatory elements from the bacterial tetracycline-resistance operon. There are two founder #36 lines. Transgene insertions are on an autosomal chromosome inthis line. [MGI Ref ID J:59444] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(tetO-MYC)36aBop, Separated PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Felsher DW; Bishop JM. 1999. Reversible tumorigenesis by MYC in hematopoietic lineages. Mol Cell 4(2):199-207. [PubMed: 10488335] [MGI Ref ID J:59444]
Additional References
Tg(tetO-MYC)36aBop relatedBeer S; Komatsubara K; Bellovin DI; Kurobe M; Sylvester K; Felsher DW. 2008. Hepatotoxin-induced changes in the adult murine liver promote MYC-induced tumorigenesis. PLoS ONE 3(6):e2493. [PubMed: 18560566] [MGI Ref ID J:139884]
Beer S; Zetterberg A; Ihrie RA; McTaggart RA; Yang Q; Bradon N; Arvanitis C; Attardi LD; Feng S; Ruebner B; Cardiff RD; Felsher DW. 2004. Developmental Context Determines Latency of MYC-Induced Tumorigenesis. PLoS Biol 2(11):E332. [PubMed: 15455033] [MGI Ref ID J:93372]
Cairo S; Armengol C; De Reynies A; Wei Y; Thomas E; Renard CA; Goga A; Balakrishnan A; Semeraro M; Gresh L; Pontoglio M; Strick-Marchand H; Levillayer F; Nouet Y; Rickman D; Gauthier F; Branchereau S; Brugieres L; Laithier V; Bouvier R; Boman F; Basso G;Michiels JF; Hofman P; Arbez-Gindre F; Jouan H; Rousselet-Chapeau MC; Berrebi D; Marcellin L; Plenat F; Zachar D; Joubert M; Selves J; Pasquier D; Bioulac-Sage P; Grotzer M; Childs M; Fabre M; Buendia MA. 2008. Hepatic stem-like phenotype and interplay of Wnt/beta-catenin and Myc signaling in aggressive childhood liver cancer. Cancer Cell 14(6):471-84. [PubMed: 19061838] [MGI Ref ID J:142029]
Cao Z; Fan-Minogue H; Bellovin DI; Yevtodiyenko A; Arzeno J; Yang Q; Gambhir SS; Felsher DW. 2011. MYC Phosphorylation, Activation, and Tumorigenic Potential in Hepatocellular Carcinoma Are Regulated by HMG-CoA Reductase. Cancer Res 71(6):2286-97. [PubMed: 21262914] [MGI Ref ID J:170758]
Chow EK; Zhang XQ; Chen M; Lam R; Robinson E; Huang H; Schaffer D; Osawa E; Goga A; Ho D. 2011. Nanodiamond therapeutic delivery agents mediate enhanced chemoresistant tumor treatment. Sci Transl Med 3(73):73ra21. [PubMed: 21389265] [MGI Ref ID J:170992]
Giuriato S; Ryeom S; Fan AC; Bachireddy P; Lynch RC; Rioth MJ; van Riggelen J; Kopelman AM; Passegue E; Tang F; Folkman J; Felsher DW. 2006. Sustained regression of tumors upon MYC inactivation requires p53 or thrombospondin-1 to reverse the angiogenic switch. Proc Natl Acad Sci U S A 103(44):16266-71. [PubMed: 17056717] [MGI Ref ID J:115637]
Goga A; Yang D; Tward AD; Morgan DO; Bishop JM. 2007. Inhibition of CDK1 as a potential therapy for tumors over-expressing MYC. Nat Med 13(7):820-7. [PubMed: 17589519] [MGI Ref ID J:125802]
Hsu SH; Wang B; Kota J; Yu J; Costinean S; Kutay H; Yu L; Bai S; La Perle K; Chivukula RR; Mao H; Wei M; Clark KR; Mendell JR; Caligiuri MA; Jacob ST; Mendell JT; Ghoshal K. 2012. Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver. J Clin Invest 122(8):2871-83. [PubMed: 22820288] [MGI Ref ID J:190067]
Hu S; Balakrishnan A; Bok RA; Anderton B; Larson PE; Nelson SJ; Kurhanewicz J; Vigneron DB; Goga A. 2011. 13C-pyruvate imaging reveals alterations in glycolysis that precede c-Myc-induced tumor formation and regression. Cell Metab 14(1):131-42. [PubMed: 21723511] [MGI Ref ID J:176076]
Jain M; Arvanitis C; Chu K; Dewey W; Leonhardt E; Trinh M; Sundberg CD; Bishop JM; Felsher DW. 2002. Sustained loss of a neoplastic phenotype by brief inactivation of MYC. Science 297(5578):102-4. [PubMed: 12098700] [MGI Ref ID J:77751]
Kampa KM; Acoba JD; Chen D; Gay J; Lee H; Beemer K; Padiernos E; Boonmark N; Zhu Z; Fan AC; Bailey AS; Fleming WH; Corless C; Felsher DW; Naumovski L; Lopez CD. 2009. Apoptosis-stimulating protein of p53 (ASPP2) heterozygous mice are tumor-prone and have attenuated cellular damage-response thresholds. Proc Natl Acad Sci U S A 106(11):4390-5. [PubMed: 19251665] [MGI Ref ID J:146764]
Kota J; Chivukula RR; O'Donnell KA; Wentzel EA; Montgomery CL; Hwang HW; Chang TC; Vivekanandan P; Torbenson M; Clark KR; Mendell JR; Mendell JT. 2009. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 137(6):1005-17. [PubMed: 19524505] [MGI Ref ID J:151413]
Lee HG; Casadesus G; Nunomura A; Zhu X; Castellani RJ; Richardson SL; Perry G; Felsher DW; Petersen RB; Smith MA. 2009. The neuronal expression of MYC causes a neurodegenerative phenotype in a novel transgenic mouse. Am J Pathol 174(3):891-7. [PubMed: 19164506] [MGI Ref ID J:146151]
Lee HG; Chen Q; Wolfram JA; Richardson SL; Liner A; Siedlak SL; Zhu X; Ziats NP; Fujioka H; Felsher DW; Castellani RJ; Valencik ML; McDonald JA; Hoit BD; Lesnefsky EJ; Smith MA. 2009. Cell cycle re-entry and mitochondrial defects in myc-mediated hypertrophic cardiomyopathy and heart failure. PLoS One 4(9):e7172. [PubMed: 19779629] [MGI Ref ID J:153600]
Morawski M; Pavlica S; Seeger G; Grosche J; Kouznetsova E; Schliebs R; Bruckner G; Arendt T. 2010. Perineuronal nets are largely unaffected in Alzheimer model Tg2576 mice. Neurobiol Aging 31(7):1254-6. [PubMed: 18829133] [MGI Ref ID J:161988]
Nielsen CH; Kimura RH; Withofs N; Tran PT; Miao Z; Cochran JR; Cheng Z; Felsher D; Kjaer A; Willmann JK; Gambhir SS. 2010. PET imaging of tumor neovascularization in a transgenic mouse model with a novel 64Cu-DOTA-knottin peptide. Cancer Res 70(22):9022-30. [PubMed: 21062977] [MGI Ref ID J:166856]
O'Donnell KA; Keng VW; York B; Reineke EL; Seo D; Fan D; Silverstein KA; Schrum CT; Xie WR; Mularoni L; Wheelan SJ; Torbenson MS; O'Malley BW; Largaespada DA; Boeke JD. 2012. A Sleeping Beauty mutagenesis screen reveals a tumor suppressor role for Ncoa2/Src-2 in liver cancer. Proc Natl Acad Sci U S A 109(21):E1377-86. [PubMed: 22556267] [MGI Ref ID J:184782]
Opavsky R; Tsai SY; Guimond M; Arora A; Opavska J; Becknell B; Kaufmann M; Walton NA; Stephens JA; Fernandez SA; Muthusamy N; Felsher DW; Porcu P; Caligiuri MA; Leone G. 2007. Specific tumor suppressor function for E2F2 in Myc-induced T cell lymphomagenesis. Proc Natl Acad Sci U S A 104(39):15400-5. [PubMed: 17881568] [MGI Ref ID J:125304]
Opavsky R; Wang SH; Trikha P; Raval A; Huang Y; Wu YZ; Rodriguez B; Keller B; Liyanarachchi S; Wei G; Davuluri RV; Weinstein M; Felsher D; Ostrowski M; Leone G; Plass C. 2007. CpG island methylation in a mouse model of lymphoma is driven by the genetic configuration of tumor cells. PLoS Genet 3(9):1757-69. [PubMed: 17907813] [MGI Ref ID J:130029]
Podsypanina K; Politi K; Beverly LJ; Varmus HE. 2008. Oncogene cooperation in tumor maintenance and tumor recurrence in mouse mammary tumors induced by Myc and mutant Kras. Proc Natl Acad Sci U S A 105(13):5242-7. [PubMed: 18356293] [MGI Ref ID J:133578]
Refaeli Y; Field KA; Turner BC; Trumpp A; Bishop JM. 2005. The protooncogene MYC can break B cell tolerance. Proc Natl Acad Sci U S A 102(11):4097-102. [PubMed: 15753301] [MGI Ref ID J:97189]
Refaeli Y; Young RM; Turner BC; Duda J; Field KA; Bishop JM. 2008. The B cell antigen receptor and overexpression of MYC can cooperate in the genesis of B cell lymphomas. PLoS Biol 6(6):e152. [PubMed: 18578569] [MGI Ref ID J:139351]
Saddic LA; Wirt S; Vogel H; Felsher DW; Sage J. 2011. Functional Interactions between Retinoblastoma and c-MYC in a Mouse Model of Hepatocellular Carcinoma. PLoS One 6(5):e19758. [PubMed: 21573126] [MGI Ref ID J:172430]
Shachaf CM; Gentles AJ; Elchuri S; Sahoo D; Soen Y; Sharpe O; Perez OD; Chang M; Mitchel D; Robinson WH; Dill D; Nolan GP; Plevritis SK; Felsher DW. 2008. Genomic and proteomic analysis reveals a threshold level of MYC required for tumor maintenance. Cancer Res 68(13):5132-42. [PubMed: 18593912] [MGI Ref ID J:138881]
Shachaf CM; Kopelman AM; Arvanitis C; Karlsson A; Beer S; Mandl S; Bachmann MH; Borowsky AD; Ruebner B; Cardiff RD; Yang Q; Bishop JM; Contag CH; Felsher DW. 2004. MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature 431(7012):1112-7. [PubMed: 15475948] [MGI Ref ID J:93899]
Tilli MT; Furth PA. 2003. Conditional mouse models demonstrate oncogene-dependent differences in tumor maintenance and recurrence. Breast Cancer Res 5(4):202-5. [PubMed: 12817992] [MGI Ref ID J:84503]
Tran PT; Bendapudi PK; Lin HJ; Choi P; Koh S; Chen J; Horng G; Hughes NP; Schwartz LH; Miller VA; Kawashima T; Kitamura T; Paik D; Felsher DW. 2011. Survival and death signals can predict tumor response to therapy after oncogene inactivation. Sci Transl Med 3(103):103ra99. [PubMed: 21974937] [MGI Ref ID J:178317]
Tran TP; Fan AC; Bendapudi PK; Koh S; Komatsubara K; Chen J; Horng G; Bellovin DI; Giuriato S; Wang CS; Whitsett JA; Felsher DW. 2008. Combined Inactivation of MYC and K-Ras oncogenes reverses tumorigenesis in lung adenocarcinomas and lymphomas. PLoS ONE 3(5):e2125. [PubMed: 18461184] [MGI Ref ID J:136212]
Traykova-Brauch M; Schonig K; Greiner O; Miloud T; Jauch A; Bode M; Felsher DW; Glick AB; Kwiatkowski DJ; Bujard H; Horst J; von Knebel Doeberitz M; Niggli FK; Kriz W; Grone HJ; Koesters R. 2008. An efficient and versatile system for acute and chronic modulation of renal tubular function in transgenic mice. Nat Med 14(9):979-84. [PubMed: 18724376] [MGI Ref ID J:140925]
Woods SL; Bishop JM. 2011. A new transgenic mouse line for tetracycline inducible transgene expression in mature melanocytes and the melanocyte stem cells using the Dopachrome tautomerase promoter. Transgenic Res 20(2):421-8. [PubMed: 20577802] [MGI Ref ID J:170027]
Young RM; Polsky A; Refaeli Y. 2009. TC-PTP is required for the maintenance of MYC-driven B-cell lymphomas. Blood 114(24):5016-23. [PubMed: 19755676] [MGI Ref ID J:155497]
van Riggelen J; Muller J; Otto T; Beuger V; Yetil A; Choi PS; Kosan C; Moroy T; Felsher DW; Eilers M. 2010. The interaction between Myc and Miz1 is required to antagonize TGFbeta-dependent autocrine signaling during lymphoma formation and maintenance. Genes Dev 24(12):1281-94. [PubMed: 20551174] [MGI Ref ID J:161202]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, hemizygous mice may be bred to wildtype (non-carrier) mice from the colony or to FVB/NJ inbred mice (as Stock No. 001800). Homozygous mice do not survive.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
This strain is currently Under Development - Now Accepting Orders.
Estimated Available for Distribution Date:
22-JUL-13
Please note: You may now place orders for this strain although it is not yet ready for distribution. Estimated available for distribution 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 distribution 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.
| Pricing for USA, Canada and Mexico shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $232.00 Female or Male Hemizygous for Tg(tetO-MYC)36aBop
Price per Pair (US dollars $) Pair Genotype $296.00 Hemizygous for Tg(tetO-MYC)36aBop x Noncarrier $296.00 Noncarrier x Hemizygous for Tg(tetO-MYC)36aBop Standard Supply
Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.
| Pricing for International shipping destinations |
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Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $301.60 Female or Male Hemizygous for Tg(tetO-MYC)36aBop
Price per Pair (US dollars $) Pair Genotype $384.80 Hemizygous for Tg(tetO-MYC)36aBop x Noncarrier $384.80 Noncarrier x Hemizygous for Tg(tetO-MYC)36aBop Standard Supply
Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.
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Standard Supply
Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | (approximate) | |
| 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.Ordering Information
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