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- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
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 Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N?+N1F2pN1
Generation DefinitionsDonating Investigator Daniel G. Tenen, Beth Israel Deaconess Medical Center Description
Hemizygotes are viable, fertile, normal in size, and do not display any behavioral abnormalities. Transgene expression is directed by the tetracycline-responsive element (TRE; tetO). When hemizygotes are bred with another transgenic mouse expressing either reverse tetracycline-controlled transactivator protein (rtTA) or tetracycline-controlled transactivator protein (tTA) under the regulation of tissue-specific promoters , BCR-ABL1 fusion protein expression can be regulated in the appropriate tissue of the bitransgenic offspring with the tetracycline analog, doxycycline.These mice originally were designed to be bred with transgenic mice harboring a Tal1-tTA transgene (see Stock No. 006209), creating double transgenic offspring as a model for studies of the Philadelphia chromosome and inducible chronic myeloid leukemia.
When bred to a strain expressing tTA in the epithelial cells of secretory organs and skin (see Stock No. 002618 - Tg(MMTVtTa)1Mam), this mutant mouse strain may be useful in studies of leukemia.
When bred to a strain expressing tTA in thebone marrow hematopoietic stem cells and in common myeloid progenitors (see Stock No. 017722 - Tg(Tal1-tTA)19Dgt), this mutant mouse strain may be useful in studies of chronic myeloid leukemia.
Development
A transgene was generated containing a human p210 BCR-ABL1 fusion protein cDNA sequence under transcriptional control of the tetracycline-responsive element (TRE; tetO) sequence fused to a minimal cytomegalovirus (hCMV) promoter. The transgene was injected into fertilized FVB/N eggs. Transgenic offspring (founder line 2) were maintained by breeding transgenic mice to either FVB/N inbred mice or wildtype siblings for many generations prior to arrival at The Jackson Laboratory.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of ABL1
017833 B6.Cg-Tg(BCR/ABL)623Hkp/J 015838 STOCK Tg(Camk2a-tTA)1Mmay Tg(tetO-ABL1*P242E*P249E)CPdav/J 014544 STOCK Tg(tetO-ABL1*P242E*P249E)CPdav/J View Strains carrying other alleles of ABL1 (3 strains)
017833 B6.Cg-Tg(BCR/ABL)623Hkp/J
Additional Web Information
Tet Expression Systems
Phenotype
Phenotype Information
- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.
Leukemia, Chronic Myeloid; CML
- 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. Leukemia, Acute Lymphoblastic; ALL (BCR)
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(tetO-BCR/ABL1)2Dgt/0 Tg(MMTVtTA)1Mam/0
involves: C57BL/6 * FVB/N * SJL
- mortality/aging
- premature death
- upon withdrawal of tetracycline (TET), expression of BCR/ABL results in development of lethal leukemia; 100% of bitransgenic mice die by ~27 days (MGI Ref ID J:72377)
- hematopoietic system phenotype
- anemia
- severe anemia develops in peripheral blood without TET treatment (MGI Ref ID J:72377)
- decreased platelet cell number
- severe thrombocytopenia in peripheral blood develops when TET treatment is stopped (MGI Ref ID J:72377)
- enlarged spleen
- spleen becomes massively enlarged when TET treatment is stopped (MGI Ref ID J:72377)
- increased leukocyte cell number
- increased peripheral blood leukocyte count is observed 6-10 days after TET withdrawal; blood shows presence of cells resembling immature lymphocytes (MGI Ref ID J:72377)
- when TET is given to mice in advanced stages of disease, WBC counts normalize in 48-72 hours, lymphoblasts are not detected in peripheral blood (MGI Ref ID J:72377)
- immune system phenotype
- enlarged lymph nodes
- nodes become massively enlarged when TET is stopped; when TET is given to mice in advanced stages of disease, complete regression of enlarged lymph nodes occurs within 5 days (MGI Ref ID J:72377)
- enlarged spleen
- spleen becomes massively enlarged when TET treatment is stopped (MGI Ref ID J:72377)
- increased leukocyte cell number
- increased peripheral blood leukocyte count is observed 6-10 days after TET withdrawal; blood shows presence of cells resembling immature lymphocytes (MGI Ref ID J:72377)
- when TET is given to mice in advanced stages of disease, WBC counts normalize in 48-72 hours, lymphoblasts are not detected in peripheral blood (MGI Ref ID J:72377)
- cellular phenotype
- increased apoptosis
- spleen becomes massively enlarged (MGI Ref ID J:72377)
- skeleton phenotype
- abnormal bone marrow morphology
- bone marrow is pale; hematopoietic cells are replaced by lymphoblasts (MGI Ref ID J:72377)
- tumorigenesis
- leukemia
Tg(tetO-BCR/ABL1)2Dgt/0 Tg(Tal1-tTA)19Dgt/0
involves: C57BL/6 * DBA/2 * FVB/N
- mortality/aging
- premature death (MGI Ref ID J:96511)
- hematopoietic system phenotype
- abnormal hematopoiesis
- 12 days after BCR/ABL induction, bone marrow shows a 7-fold increase in hematopoietic stem cells and a 26-fold increase after 21 days; at both points, granulocyte-macrophage progenitor (GMP) percentage is increased 3-fold, while megakaryocyte-erythroid progenitors (MEP) show a 3-fold decrease (MGI Ref ID J:96511)
- abnormal common myeloid progenitor cell morphology
- common myeloid precursors (CMP) show a 2-fold decrease and a 1.5-fold increase at 12 and 21 days, respectively (MGI Ref ID J:96511)
- abnormal lymphopoiesis
- some mice (31%) show progression to lymphoid blast crisis with lymph node enlargement and lymphoblasts in peripheral blood; lymphooblasts are found to be arrested at different maturation stages (MGI Ref ID J:96511)
- increased leukocyte cell number
- increased neutrophil cell number
- percentage and absolute number of neutrophils are increased 3- and 5- fold in peripheral blood 2 weeks after tetracycline (tet) withdrawal compared to wild-type or single transgenic mice (MGI Ref ID J:96511)
- readministration of tet results in reversion of neutrophilia in approximately ~4 days (MGI Ref ID J:96511)
- abnormal myeloblast morphology/development
- abnormal lymphopoiesis
- some mice (31%) show progression to lymphoid blast crisis with lymph node enlargement and lymphoblasts in peripheral blood; lymphooblasts are found to be arrested at different maturation stages (MGI Ref ID J:96511)
- abnormal spleen red pulp morphology
- after induction of BCR/ABL expression, expansion of spleen red pulp by granulocytic myeloid cells is observed at various time points (MGI Ref ID J:96511)
- abnormal splenic cell ratio
- induction of BCR/ABL increases numbers of erythroid and granulocytic-monocytic progenitor cells in spleen (MGI Ref ID J:96511)
- enlarged spleen
- increased bone marrow cell number
- increased hematopoietic stem cell number
- 12 days after BCR/ABL induction, bone marrow shows a 7-fold increase in hematopoietic stem cells (MGI Ref ID J:96511)
- increased megakaryocyte cell number
- increased numbers of megakaryocytes are detected in bone marrow and spleen of diseased mice (MGI Ref ID J:96511)
- immune system phenotype
- abnormal lymph node morphology
- infiltration by myeloid cells is observed (MGI Ref ID J:96511)
- abnormal lymphopoiesis
- some mice (31%) show progression to lymphoid blast crisis with lymph node enlargement and lymphoblasts in peripheral blood; lymphooblasts are found to be arrested at different maturation stages (MGI Ref ID J:96511)
- abnormal spleen red pulp morphology
- after induction of BCR/ABL expression, expansion of spleen red pulp by granulocytic myeloid cells is observed at various time points (MGI Ref ID J:96511)
- abnormal splenic cell ratio
- induction of BCR/ABL increases numbers of erythroid and granulocytic-monocytic progenitor cells in spleen (MGI Ref ID J:96511)
- enlarged spleen
- increased leukocyte cell number
- increased neutrophil cell number
- percentage and absolute number of neutrophils are increased 3- and 5- fold in peripheral blood 2 weeks after tetracycline (tet) withdrawal compared to wild-type or single transgenic mice (MGI Ref ID J:96511)
- readministration of tet results in reversion of neutrophilia in approximately ~4 days (MGI Ref ID J:96511)
- liver/biliary system phenotype
- enlarged liver
- infiltration of liver by myeloid cells is observed after induction; 57% of mice display hepatomegaly (MGI Ref ID J:96511)
- respiratory system phenotype
- abnormal lung morphology
- infiltration by myeloid cells is observed, occasionally resulting in focal pulmonary hemorrhages (MGI Ref ID J:96511)
- digestive/alimentary phenotype
- abnormal small intestine morphology
- infiltration of lamina propria by myeloid cells is observed (MGI Ref ID J:96511)
- tumorigenesis
- increased lymphoma incidence
- sarcoma
- 2 animals with fulminant disease displayed skin chloromas (granulocytic sarcomas) (MGI Ref ID J:96511)
- cellular phenotype
- abnormal lymphopoiesis
- some mice (31%) show progression to lymphoid blast crisis with lymph node enlargement and lymphoblasts in peripheral blood; lymphooblasts are found to be arrested at different maturation stages (MGI Ref ID J:96511)
This mouse can be used to support research in many areas including:
Cancer Research
Chronic Myelogenous Leukemia
Increased Tumor Incidence
Leukemia
Leukemia: lymphocytic
Hematological Research
Hematopoietic Defects
Immunological Defects
Immunology, Inflammation and Autoimmunity Research
Lymphoid Tissue Defects
hematopoietic development
myeloid hyperplasia
Research Tools
Cancer Research
Leukemia
Tetop Tet System
myeloma and hybridoma production
Hematological Research
Tet Expression Systems
tTA/rtTA Responsive Strains
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(tetO-BCR/ABL1)2Dgt | ||
|---|---|---|---|
| Allele Name | transgene insertion 2, Daniel G Tenen | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | BCR-ABL; BCR-ABL stg; BCR-ABL1; TRE-BCR-ABL; TRE-BCR/ABL; TRE-P10 BCR/ABL; TRE-p210-BCR-ABL; Tg(BCR/ABL1)2Dgt; Tg(BCR/ABL1)3Dgt; p210 BCR-ABL1 transponder; p210-BCR-ABL; | ||
| Mutation Made By | Daniel Tenen, Beth Israel Deaconess Medical Center | ||
| Strain of Origin | FVB/N | ||
| Expressed Gene | ABL1, c-abl oncogene 1, non-receptor tyrosine kinase, human | ||
| Expressed Gene | BCR, breakpoint cluster region, human | ||
| Promoter | tetO, tet operator, | ||
| General Note | This record is also representative of lines 3 and 4 that were also generated; all of these lines exhibit a similar phenotype in combination with Tg(MMTVtTA)1Mam.Bitransgenic mice with this transgene in combination with Tg(MMTVtTA)1Mam, when tetracycline administration is stopped, are models for B cell acute lymphoblastic leukemia (ALL); line 2 exhibits the greatest leukemia susceptibility (Figure 1). (J:72377) | ||
| Molecular Note | The transgene contains a cDNA encoding the human p210 BCR-ABL1 fusion protein (B3A2 form; J:86227) under transcriptional control of the tetracycline-responsive element (tetO; also called TRE) fused to a minimal cytomegalovirus (CMV) promoter. In doubly transgenic mice expressing a tetracycline transactivator or reverse transactivator protein under control of a ubiquitous or tissue-specific promoter, expression of the BCL-ABL1 fusion gene can be controlled temporally by withdrawal or administration of a tetracycline analog. [MGI Ref ID J:72377] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(tetO-BCR/ABL1)2Dgt, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Huettner CS; Zhang P; Van Etten RA; Tenen DG. 2000. Reversibility of acute B-cell leukaemia induced by BCR-ABL1. Nat Genet 24(1):57-60. [PubMed: 10615128] [MGI Ref ID J:72377]
Additional References
Tg(tetO-BCR/ABL1)2Dgt relatedChen CI; Koschmieder S; Kerstiens L; Schemionek M; Altvater B; Pscherer S; Gerss J; Maecker HT; Berdel WE; Juergens H; Lee PP; Rossig C. 2012. NK cells are dysfunctional in human chronic myelogenous leukemia before and on imatinib treatment and in BCR-ABL-positive mice. Leukemia 26(3):465-74. [PubMed: 21904381] [MGI Ref ID J:181529]
Eiring AM; Harb JG; Neviani P; Garton C; Oaks JJ; Spizzo R; Liu S; Schwind S; Santhanam R; Hickey CJ; Becker H; Chandler JC; Andino R; Cortes J; Hokland P; Huettner CS; Bhatia R; Roy DC; Liebhaber SA; Caligiuri MA; Marcucci G; Garzon R; Croce CM; Calin GA; Perrotti D. 2010. miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts. Cell 140(5):652-65. [PubMed: 20211135] [MGI Ref ID J:160777]
Hamilton A; Helgason GV; Schemionek M; Zhang B; Myssina S; Allan EK; Nicolini FE; Muller-Tidow C; Bhatia R; Brunton VG; Koschmieder S; Holyoake TL. 2012. Chronic myeloid leukemia stem cells are not dependent on Bcr-Abl kinase activity for their survival. Blood 119(6):1501-10. [PubMed: 22184410] [MGI Ref ID J:181724]
Huettner CS; Koschmieder S; Iwasaki H; Iwasaki-Arai J; Radomska HS; Akashi K; Tenen DG. 2003. Inducible expression of BCR/ABL using human CD34 regulatory elements results in a megakaryocytic myeloproliferative syndrome. Blood 102(9):3363-70. [PubMed: 12855552] [MGI Ref ID J:86227]
Koschmieder S; Gottgens B; Zhang P; Iwasaki-Arai J; Akashi K; Kutok JL; Dayaram T; Geary K; Green AR; Tenen DG; Huettner CS. 2005. Inducible chronic phase of myeloid leukemia with expansion of hematopoietic stem cells in a transgenic model of BCR-ABL leukemogenesis. Blood 105(1):324-34. [PubMed: 15331442] [MGI Ref ID J:96511]
Reynaud D; Pietras E; Barry-Holson K; Mir A; Binnewies M; Jeanne M; Sala-Torra O; Radich JP; Passegue E. 2011. IL-6 controls leukemic multipotent progenitor cell fate and contributes to chronic myelogenous leukemia development. Cancer Cell 20(5):661-73. [PubMed: 22094259] [MGI Ref ID J:178950]
Schemionek M; Elling C; Steidl U; Baumer N; Hamilton A; Spieker T; Gothert JR; Stehling M; Wagers A; Huettner CS; Tenen DG; Tickenbrock L; Berdel WE; Serve H; Holyoake TL; Muller-Tidow C; Koschmieder S. 2010. BCR-ABL enhances differentiation of long-term repopulating hematopoietic stem cells. Blood 115(16):3185-95. [PubMed: 20053753] [MGI Ref ID J:160797]
Schemionek M; Spieker T; Kerstiens L; Elling C; Essers M; Trumpp A; Berdel WE; Muller-Tidow C; Koschmieder S. 2012. Leukemic spleen cells are more potent than bone marrow-derived cells in a transgenic mouse model of CML. Leukemia 26(5):1030-7. [PubMed: 22193968] [MGI Ref ID J:188980]
Sengupta A; Arnett J; Dunn S; Williams DA; Cancelas JA. 2010. Rac2 GTPase deficiency depletes BCR-ABL+ leukemic stem cells and progenitors in vivo. Blood 116(1):81-4. [PubMed: 20407032] [MGI Ref ID J:162808]
Sengupta A; Ficker AM; Dunn SK; Madhu M; Cancelas JA. 2012. Bmi1 reprograms CML B-lymphoid progenitors to become B-ALL-initiating cells. Blood 119(2):494-502. [PubMed: 22101899] [MGI Ref ID J:181793]
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]
Zhang B; Strauss AC; Chu S; Li M; Ho Y; Shiang KD; Snyder DS; Huettner CS; Shultz L; Holyoake T; Bhatia R. 2010. Effective targeting of quiescent chronic myelogenous leukemia stem cells by histone deacetylase inhibitors in combination with imatinib mesylate. Cancer Cell 17(5):427-42. [PubMed: 20478526] [MGI Ref ID J:160523]
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 & Husbandry When maintaining a live colony, transgenic mice are bred together or to wildtype siblings.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2250.00 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 |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2925.00 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).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
General Supply Notes
- Genomic DNA is available for this strain from the Mouse DNA Resource.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
See Terms of Use tab for General Terms and Conditions
The Jackson Laboratory's Genotype Promise
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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For Licensing and Use Restrictions view the link(s) below:
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Contact information
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JAX® Mice, Products & Services Conditions of Use
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