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- Description
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- Genes & alleles
- Genotyping
- Health & husbandry
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Description
Strain Information
Type Coisogenic; Mutant Strain; Transgenic; Mating System +/+ sibling x Hemizygote (Female x Male) Species laboratory mouse Generation N?+N1F3 (24-APR-08) Donating Investigator Daniel 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.
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 tetO
View Strains carrying other alleles of tetO (28 strains)
Additional Web Information
Tet Expression Systems
Phenotype
Phenotype Information
Related Disease (OMIM) Terms
Leukemia, Chronic Myeloid; CML Mammalian Phenotype Terms 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
- life span-post-weaning/aging
- premature death (MGI Ref ID J:72377)
- upon withdrawal of tetracycline (TET), expression of BCR/ABL results in development of lethal leukemia; 100% of bitransgenic mice die by ~27 days
- hematopoietic system phenotype
- anemia (MGI Ref ID J:72377)
- severe anemia develops in peripheral blood without TET treatment
- decreased platelet cell number (MGI Ref ID J:72377)
- severe thrombocytopenia in peripheral blood develops when TET treatment is stopped
- enlarged spleen (MGI Ref ID J:72377)
- spleen becomes massively enlarged when TET treatment is stopped
- increased leukocyte cell number (MGI Ref ID J:72377)
- increased peripheral blood leukocyte count is observed 6-10 days after TET withdrawal; blood shows presence of cells resembling immature lymphocytes
- 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
- immune system phenotype
- enlarged lymph nodes (MGI Ref ID J:72377)
- 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
- enlarged spleen (MGI Ref ID J:72377)
- spleen becomes massively enlarged when TET treatment is stopped
- increased leukocyte cell number (MGI Ref ID J:72377)
- increased peripheral blood leukocyte count is observed 6-10 days after TET withdrawal; blood shows presence of cells resembling immature lymphocytes
- 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
- cellular phenotype
- increased apoptosis (MGI Ref ID J:72377)
- spleen becomes massively enlarged
- skeleton phenotype
- abnormal bone marrow morphology (MGI Ref ID J:72377)
- bone marrow is pale; hematopoietic cells are replaced by lymphoblasts
- tumorigenesis
- leukemia (MGI Ref ID J:72377)
- 100% of mice develop acute lymphoblastic leukemia (ALL) upon withdrawal of tetracycline administration
- leukocyte counts range from 80000-150000/ul
- leukemic cells infiltrate skin, pleura, and meninges
Tg(tetO-BCR/ABL1)2Dgt/0 Tg(Tal1-tTA)19Dgt/0
involves: C57BL/6 * DBA/2 * FVB/N
- life span-post-weaning/aging
- premature death (MGI Ref ID J:96511)
- hematopoietic system phenotype
- abnormal hematopoiesis (MGI Ref ID J:96511)
- 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
- abnormal common myeloid progenitor cell morphology (MGI Ref ID J:96511)
- common myeloid precursors (CMP) show a 2-fold decrease and a 1.5-fold increase at 12 and 21 days, respectively
- abnormal lymphopoiesis (MGI Ref ID J:96511)
- 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
- increased leukocyte cell number (MGI Ref ID J:96511)
- absolute number is increased 2-fold in peripheral blood 2 weeks after tet withdrawal (BCR/ABL induction)
- readministration of tet results in reversion of leukocytosis in approximately ~4 days
- increased neutrophil cell number (MGI Ref ID J:96511)
- 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
- readministration of tet results in reversion of neutrophilia in approximately ~4 days
- abnormal myeloblast morphology/development (MGI Ref ID J:96511)
- bone marrow contains increased ratio of myeloid and erythroid cells dominated by granulocytic forms
- increase in immature myeloid cells is observed
- abnormal lymphopoiesis (MGI Ref ID J:96511)
- 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
- abnormal spleen cellularity (MGI Ref ID J:96511)
- induction of BCR/ABL increases numbers of erythroid and granulocytic-monocytic progenitor cells in spleen
- abnormal spleen red pulp morphology (MGI Ref ID J:96511)
- after induction of BCR/ABL expression, expansion of spleen red pulp by granulocytic myeloid cells is observed at various time points
- enlarged spleen (MGI Ref ID J:96511)
- after induction by withdrawal of tet treatment, splenomegaly invariably results
- readministration of tet results in disappearance of palpable splenomegaly
- increased bone marrow cell number (MGI Ref ID J:96511)
- bone marrow of diseased mice is hypercellular
- increased numbers of cells of lymphoid and myeloid lineage are detected in diseased mice
- increased hematopoietic stem cell number (MGI Ref ID J:96511)
- 12 days after BCR/ABL induction, bone marrow shows a 7-fold increase in hematopoietic stem cells
- increased megakaryocyte cell number (MGI Ref ID J:96511)
- increased numbers of megakaryocytes are detected in bone marrow and spleen of diseased mice
- immune system phenotype
- abnormal lymph node morphology (MGI Ref ID J:96511)
- infiltration by myeloid cells is observed
- abnormal lymphopoiesis (MGI Ref ID J:96511)
- 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
- abnormal spleen cellularity (MGI Ref ID J:96511)
- induction of BCR/ABL increases numbers of erythroid and granulocytic-monocytic progenitor cells in spleen
- abnormal spleen red pulp morphology (MGI Ref ID J:96511)
- after induction of BCR/ABL expression, expansion of spleen red pulp by granulocytic myeloid cells is observed at various time points
- enlarged spleen (MGI Ref ID J:96511)
- after induction by withdrawal of tet treatment, splenomegaly invariably results
- readministration of tet results in disappearance of palpable splenomegaly
- increased leukocyte cell number (MGI Ref ID J:96511)
- absolute number is increased 2-fold in peripheral blood 2 weeks after tet withdrawal (BCR/ABL induction)
- readministration of tet results in reversion of leukocytosis in approximately ~4 days
- increased neutrophil cell number (MGI Ref ID J:96511)
- 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
- readministration of tet results in reversion of neutrophilia in approximately ~4 days
- liver/biliary system phenotype
- enlarged liver (MGI Ref ID J:96511)
- infiltration of liver by myeloid cells is observed after induction; 57% of mice display hepatomegaly
- respiratory system phenotype
- abnormal lung morphology (MGI Ref ID J:96511)
- infiltration by myeloid cells is observed, occasionally resulting in focal pulmonary hemorrhages
- digestive/alimentary phenotype
- abnormal small intestine morphology (MGI Ref ID J:96511)
- infiltration of lamina propria by myeloid cells is observed
- tumorigenesis
- lymphoma (MGI Ref ID J:96511)
- some mice develop lymphomas
- readministration of tet results in disappearance of lymphomas (except in 1 case)
- sarcoma (MGI Ref ID J:96511)
- 2 animals with fulminant disease displayed skin chloromas (granulocytic sarcomas)
Research Applications
This mouse can be used to support research in many areas including:
Cancer Research
Chronic Myelogenous Leukemia
Increased Tumor Incidence (Leukemia: lymphocytic)
Hematological Research
Hematopoietic Defects
Immunological Defects
Immunology and Inflammation Research
Lymphoid Tissue Defects (hematopoietic development)
Lymphoid Tissue Defects (myeloid hyperplasia)
Research Tools
Cancer Research (Leukemia)
Cancer Research (Tetop Tet System)
Cancer Research (myeloma and hybridoma production)
Hematological Research
Tet Expression Systems (tTA/rtTA Responsive Strains)
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(tetO-BCR/ABL1)2Dgt | ||
|---|---|---|---|
| Allele Name | transgene insertion 2, Daniel G Tenen | ||
| Common Name(s) | BCR-ABL1; TRE-BCR-ABL; TRE-BCR/ABL; TRE-P10 BCR/ABL; Tg(BCR/ABL1)2Dgt; Tg(BCR/ABL1)3Dgt; p210 BCR-ABL1 transponder; | ||
| Mutation Made By | Daniel Tenen, Beth Israel Deaconess Medical Center | ||
| Strain of Origin | FVB/N | ||
| Expressed Gene | ABL1, c-abl oncogene 1, 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, HRM, vers. 2
Tg(tetO-BCR/ABL1)2Dgt, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
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 related
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]
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]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, transgenic mice are bred together or to wildtype siblings. Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
Pricing for USA, Canada and Mexico shipping destinations
View International Pricing
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $203.80 Female or Male Hemizygous for Tg(tetO-BCR/ABL1)2Dgt *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $256.05 Hemizygous for Tg(tetO-BCR/ABL1)2Dgt x Noncarrier $256.05 Noncarrier x Hemizygous for Tg(tetO-BCR/ABL1)2Dgt
Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
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| Supply Notes |
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Pricing for International shipping destinations
View USA, Canada and Mexico Pricing
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $265.00 Female or Male Hemizygous for Tg(tetO-BCR/ABL1)2Dgt *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $332.90 Hemizygous for Tg(tetO-BCR/ABL1)2Dgt x Noncarrier $332.90 Noncarrier x Hemizygous for Tg(tetO-BCR/ABL1)2Dgt
Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| 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. | ||
General Terms and Conditions
View JAX® Mice & Services Conditions of Use.
Use of the Tet-System may require a license, see Licenses for Strains Using TET-System Technology.
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 and Purchasing Information
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