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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Tg(tetO-BCR/ABL1)2Dgt
transgene insertion 2, Daniel G Tenen
MGI:2387680
Summary 5 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cn1
Gt(ROSA)26Sortm4(CAG-hsb5)Nki/Gt(ROSA)26Sor+
Tg(Mx1-cre)1Cgn/0
Tg(Tal1-tTA)19Dgt/0
Tg(tetO-BCR/ABL1)2Dgt/0
TgTn(pb-sb-GrOnc)#aGsva/0
involves: 129P2/OlaHsd * C57BL/6 * CBA/J * DBA/2 * FVB/N MGI:5806781
cn2
Gt(ROSA)26Sortm4(CAG-hsb5)Nki/Gt(ROSA)26Sor+
Tg(Mx1-cre)1Cgn/0
Tg(tetO-BCR/ABL1)2Dgt/0
TgTn(pb-sb-GrOnc)#aGsva/0
involves: 129P2/OlaHsd * C57BL/6 * CBA/J * FVB/N MGI:5806786
cx3
Tg(Mx1-cre)1Cgn/0
Tg(Tal1-tTA)19Dgt/0
Tg(tetO-BCR/ABL1)2Dgt/0
TgTn(pb-sb-GrOnc)#aGsva/0
involves: C57BL/6 * CBA/J * DBA/2 * FVB/N MGI:5806784
cx4
Tg(tetO-BCR/ABL1)2Dgt/0
Tg(Tal1-tTA)19Dgt/0
involves: C57BL/6 * DBA/2 * FVB/N MGI:3693373
cx5
Tg(tetO-BCR/ABL1)2Dgt/0
Tg(MMTVtTA)1Mam/0
involves: C57BL/6 * FVB/N * SJL MGI:3693361


Genotype
MGI:5806781
cn1
Allelic
Composition
Gt(ROSA)26Sortm4(CAG-hsb5)Nki/Gt(ROSA)26Sor+
Tg(Mx1-cre)1Cgn/0
Tg(Tal1-tTA)19Dgt/0
Tg(tetO-BCR/ABL1)2Dgt/0
TgTn(pb-sb-GrOnc)#aGsva/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6 * CBA/J * DBA/2 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm4(CAG-hsb5)Nki mutation (0 available); any Gt(ROSA)26Sor mutation (512 available)
Tg(Mx1-cre)1Cgn mutation (6 available)
Tg(Tal1-tTA)19Dgt mutation (2 available)
Tg(tetO-BCR/ABL1)2Dgt mutation (1 available)
TgTn(pb-sb-GrOnc)#aGsva mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mice withdrawn from tetracycline and treated with polyinosine-polycyticylic acid (pIpC) show a decrease in survival with median survival of 116.5 days

neoplasm
• majority of pIpC treated mice (85%) develop an exclusively myeloid and primary acute leukemia phenotype
• 5% of mice remain in the chronic phase of the disease
• about 10% of mice develop an accelerated phase-like phenotype but with less than 20% blasts
• however, mice do not develop lymphoid leukemias

hematopoietic system
• hemoglobin levels are decreased in pIpC treated mice
• upon withdrawal of tetracycline and treatment with pIpC, mice develop moderate, but persistent (2-3 fold) increase of white blood counts
• white blood cell counts at the terminal endpoint are elevated, indicating a dramatic preterminal proliferative change in kinetics of their disease
• upon withdrawal of tetracycline and treatment with pIpC, mice show marked expansion of the granulocyte compartment
• increase in infiltration of tissues with both granulocytes and immature cells
• disease progression in in pIpC treated mice is frequently accompanied by an increase in basophils
• the myeloid progenitor compartment is expanded in pIpC treated mice, including the granulocyte monocyte progenitor compartment
• expansion of the lineage-negative (Lin-) bone marrow fraction in pIpC treated mice
• however, no differences are seen in total Lin-Sca+c-kit+ (LSK) numbers, long-term and short-term hematopoietic stem cell or multipotent progenitor proportions
• in pIpC treated mice
• hematopoietic stem cells show an increased ability to serially replate compared to control cells

immune system
• upon withdrawal of tetracycline and treatment with pIpC, mice develop moderate, but persistent (2-3 fold) increase of white blood counts
• white blood cell counts at the terminal endpoint are elevated, indicating a dramatic preterminal proliferative change in kinetics of their disease
• upon withdrawal of tetracycline and treatment with pIpC, mice show marked expansion of the granulocyte compartment
• increase in infiltration of tissues with both granulocytes and immature cells
• disease progression in in pIpC treated mice is frequently accompanied by an increase in basophils
• in pIpC treated mice

liver/biliary system
• in pIpC treated mice

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
chronic myeloid leukemia DOID:8552 OMIM:608232
J:227558




Genotype
MGI:5806786
cn2
Allelic
Composition
Gt(ROSA)26Sortm4(CAG-hsb5)Nki/Gt(ROSA)26Sor+
Tg(Mx1-cre)1Cgn/0
Tg(tetO-BCR/ABL1)2Dgt/0
TgTn(pb-sb-GrOnc)#aGsva/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6 * CBA/J * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm4(CAG-hsb5)Nki mutation (0 available); any Gt(ROSA)26Sor mutation (512 available)
Tg(Mx1-cre)1Cgn mutation (6 available)
Tg(tetO-BCR/ABL1)2Dgt mutation (1 available)
TgTn(pb-sb-GrOnc)#aGsva mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mice withdrawn from tetracycline and treated with polyinosine-polycyticylic acid (pIpC) show a median survival of 125.5 days

neoplasm
• 26% of mice treated with pIpC develop lymphoid acute leukemias
• 70% of mice treated with pIpC develop myeloid acute leukemias
• increase in infiltration of tissues with immature cells




Genotype
MGI:5806784
cx3
Allelic
Composition
Tg(Mx1-cre)1Cgn/0
Tg(Tal1-tTA)19Dgt/0
Tg(tetO-BCR/ABL1)2Dgt/0
TgTn(pb-sb-GrOnc)#aGsva/0
Genetic
Background
involves: C57BL/6 * CBA/J * DBA/2 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Mx1-cre)1Cgn mutation (6 available)
Tg(Tal1-tTA)19Dgt mutation (2 available)
Tg(tetO-BCR/ABL1)2Dgt mutation (1 available)
TgTn(pb-sb-GrOnc)#aGsva mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• median survival of 149 days

neoplasm
• all mice remain in the chronic phase of myeloid leukemia

hematopoietic system
• upon withdrawal of tetracycline, mice develop moderate, but persistent (2-3 fold) increase of white blood counts
• upon withdrawal of tetracycline, mice show marked expansion of the granulocyte compartment

immune system
• upon withdrawal of tetracycline, mice develop moderate, but persistent (2-3 fold) increase of white blood counts
• upon withdrawal of tetracycline, mice show marked expansion of the granulocyte compartment




Genotype
MGI:3693373
cx4
Allelic
Composition
Tg(tetO-BCR/ABL1)2Dgt/0
Tg(Tal1-tTA)19Dgt/0
Genetic
Background
involves: C57BL/6 * DBA/2 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Tal1-tTA)19Dgt mutation (2 available)
Tg(tetO-BCR/ABL1)2Dgt mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging

hematopoietic system
• 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
• common myeloid precursors (CMP) show a 2-fold decrease and a 1.5-fold increase at 12 and 21 days, respectively
• 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
• bone marrow of diseased mice is hypercellular
• increased numbers of cells of lymphoid and myeloid lineage are detected in diseased mice
• increased numbers of megakaryocytes are detected in bone marrow and spleen of diseased mice
• bone marrow contains increased ratio of myeloid and erythroid cells dominated by granulocytic forms
• increase in immature myeloid cells is observed
• 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
• 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
• 12 days after BCR/ABL induction, bone marrow shows a 7-fold increase in hematopoietic stem cells
• after induction of BCR/ABL expression, expansion of spleen red pulp by granulocytic myeloid cells is observed at various time points
• after induction by withdrawal of tet treatment, splenomegaly invariably results
• readministration of tet results in disappearance of palpable splenomegaly
• induction of BCR/ABL increases numbers of erythroid and granulocytic-monocytic progenitor cells in spleen

immune system
• 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
• 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
• 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
• after induction of BCR/ABL expression, expansion of spleen red pulp by granulocytic myeloid cells is observed at various time points
• after induction by withdrawal of tet treatment, splenomegaly invariably results
• readministration of tet results in disappearance of palpable splenomegaly
• induction of BCR/ABL increases numbers of erythroid and granulocytic-monocytic progenitor cells in spleen
• infiltration by myeloid cells is observed

liver/biliary system
• infiltration of liver by myeloid cells is observed after induction; 57% of mice display hepatomegaly

respiratory system
• infiltration by myeloid cells is observed, occasionally resulting in focal pulmonary hemorrhages

digestive/alimentary system
• infiltration of lamina propria by myeloid cells is observed

neoplasm
• some mice develop lymphomas
• readministration of tet results in disappearance of lymphomas (except in 1 case)
• 2 animals with fulminant disease displayed skin chloromas (granulocytic sarcomas)

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
chronic myeloid leukemia DOID:8552 OMIM:608232
J:96511




Genotype
MGI:3693361
cx5
Allelic
Composition
Tg(tetO-BCR/ABL1)2Dgt/0
Tg(MMTVtTA)1Mam/0
Genetic
Background
involves: C57BL/6 * FVB/N * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(MMTVtTA)1Mam mutation (2 available)
Tg(tetO-BCR/ABL1)2Dgt mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 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
• severe anemia develops in peripheral blood without TET treatment
• severe thrombocytopenia in peripheral blood develops when TET treatment is stopped
• 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
• spleen becomes massively enlarged when TET treatment is stopped

immune system
• 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
• spleen becomes massively enlarged when TET treatment is stopped
• 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

cellular
• spleen becomes massively enlarged

skeleton
• bone marrow is pale; hematopoietic cells are replaced by lymphoblasts

neoplasm
• 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





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last database update
02/11/2020
MGI 6.14
The Jackson Laboratory