Phenotypes associated with this allele

• Allele Symbol: Tg(tetO-BCR/ABL1)2Dgt
• Allele Name: transgene insertion 2, Daniel G Tenen
• Allele ID: MGI:2387680
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Gt(ROSA)26Sor^tm4(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)26Sor^tm4(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)26Sor^{tm4(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

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:227558 )

• mice withdrawn from tetracycline and treated with polyinosine-polycyticylic acid (pIpC) show a decrease in survival with median survival of 116.5 days

neoplasm

increased chronic myelocytic leukemia incidence ( J:227558 )

• 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

increased spleen weight ( J:227558 )

• in pIpC treated mice

decreased hemoglobin content ( J:227558 )

• hemoglobin levels are decreased in pIpC treated mice

increased leukocyte cell number ( J:227558 )

• 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

increased granulocyte number ( J:227558 )

• 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

increased basophil cell number ( J:227558 )

• disease progression in in pIpC treated mice is frequently accompanied by an increase in basophils

increased myeloid cell number ( J:227558 )

• the myeloid progenitor compartment is expanded in pIpC treated mice, including the granulocyte monocyte progenitor compartment

increased hematopoietic stem cell number ( J:227558 )

• 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

abnormal hematopoietic stem cell physiology ( J:227558 )

• hematopoietic stem cells show an increased ability to serially replate compared to control cells

immune system

increased spleen weight ( J:227558 )

• in pIpC treated mice

increased leukocyte cell number ( J:227558 )

• 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

increased granulocyte number ( J:227558 )

• 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

increased basophil cell number ( J:227558 )

• disease progression in in pIpC treated mice is frequently accompanied by an increase in basophils

liver/biliary system

increased liver weight ( J:227558 )

• in pIpC treated mice

growth/size/body

increased liver weight ( J:227558 )

• in pIpC treated mice

increased spleen weight ( J:227558 )

• 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)26Sor^{tm4(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

mortality/aging

premature death ( J:227558 )

• mice withdrawn from tetracycline and treated with polyinosine-polycyticylic acid (pIpC) show a median survival of 125.5 days

neoplasm

increased leukemia incidence ( J:227558 )

• 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

mortality/aging

premature death ( J:227558 )

• median survival of 149 days

neoplasm

increased chronic myelocytic leukemia incidence ( J:227558 )

• all mice remain in the chronic phase of myeloid leukemia

hematopoietic system

increased leukocyte cell number ( J:227558 )

• upon withdrawal of tetracycline, mice develop moderate, but persistent (2-3 fold) increase of white blood counts

increased granulocyte number ( J:227558 )

• upon withdrawal of tetracycline, mice show marked expansion of the granulocyte compartment

immune system

increased leukocyte cell number ( J:227558 )

• upon withdrawal of tetracycline, mice develop moderate, but persistent (2-3 fold) increase of white blood counts

increased granulocyte number ( J:227558 )

• 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

mortality/aging

premature death ( J:96511 )

hematopoietic system

enlarged spleen ( J:96511 )

• after induction by withdrawal of tet treatment, splenomegaly invariably results

• readministration of tet results in disappearance of palpable splenomegaly

abnormal definitive hematopoiesis ( 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 ( 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 ( 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 bone marrow cell number ( J:96511 )

• bone marrow of diseased mice is hypercellular

• increased numbers of cells of lymphoid and myeloid lineage are detected in diseased mice

increased megakaryocyte cell number ( J:96511 )

• increased numbers of megakaryocytes are detected in bone marrow and spleen of diseased mice

abnormal myeloblast morphology/development ( J:96511 )

• bone marrow contains increased ratio of myeloid and erythroid cells dominated by granulocytic forms

• increase in immature myeloid cells is observed

increased leukocyte cell number ( 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 ( 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

increased hematopoietic stem cell number ( J:96511 )

• 12 days after BCR/ABL induction, bone marrow shows a 7-fold increase in hematopoietic stem cells

abnormal spleen red pulp morphology ( J:96511 )

• after induction of BCR/ABL expression, expansion of spleen red pulp by granulocytic myeloid cells is observed at various time points

abnormal splenic cell ratio ( J:96511 )

• induction of BCR/ABL increases numbers of erythroid and granulocytic-monocytic progenitor cells in spleen

immune system

enlarged spleen ( J:96511 )

• after induction by withdrawal of tet treatment, splenomegaly invariably results

• readministration of tet results in disappearance of palpable splenomegaly

abnormal lymphopoiesis ( 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 ( 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 ( 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 spleen red pulp morphology ( J:96511 )

• after induction of BCR/ABL expression, expansion of spleen red pulp by granulocytic myeloid cells is observed at various time points

abnormal splenic cell ratio ( J:96511 )

• induction of BCR/ABL increases numbers of erythroid and granulocytic-monocytic progenitor cells in spleen

abnormal lymph node morphology ( J:96511 )

• infiltration by myeloid cells is observed

liver/biliary system

enlarged liver ( J:96511 )

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

respiratory system

abnormal lung morphology ( J:96511 )

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

digestive/alimentary system

abnormal small intestine morphology ( J:96511 )

• infiltration of lamina propria by myeloid cells is observed

neoplasm

increased lymphoma incidence ( J:96511 )

• some mice develop lymphomas

• readministration of tet results in disappearance of lymphomas (except in 1 case)

increased sarcoma incidence ( J:96511 )

• 2 animals with fulminant disease displayed skin chloromas (granulocytic sarcomas)

growth/size/body

enlarged liver ( J:96511 )

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

enlarged spleen ( J:96511 )

• after induction by withdrawal of tet treatment, splenomegaly invariably results

• readministration of tet results in disappearance of palpable splenomegaly

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

mortality/aging

premature death ( 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

enlarged spleen ( J:72377 )

• spleen becomes massively enlarged when TET treatment is stopped

anemia ( J:72377 )

• severe anemia develops in peripheral blood without TET treatment

thrombocytopenia ( J:72377 )

• severe thrombocytopenia in peripheral blood develops when TET treatment is stopped

increased leukocyte cell number ( 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

enlarged spleen ( J:72377 )

• spleen becomes massively enlarged when TET treatment is stopped

increased leukocyte cell number ( 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

enlarged lymph nodes ( 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

cellular

increased apoptosis ( J:72377 )

• spleen becomes massively enlarged

skeleton

abnormal bone marrow morphology ( J:72377 )

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

neoplasm

increased leukemia incidence ( 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

growth/size/body

enlarged spleen ( J:72377 )

• spleen becomes massively enlarged when TET treatment is stopped