Tg(tetO-BCR/ABL1)2Dgt Transgene Detail MGI Mouse (MGI:2387680)

Tg(tetO-BCR/ABL1)2Dgt
Transgene Detail

Nomenclature

Symbol:	Tg(tetO-BCR/ABL1)2Dgt
Name:	transgene insertion 2, Daniel G Tenen
MGI ID:	MGI:2387680
Synonyms:	BCR-ABL1, p210 BCR-ABL1 transponder, Tg(BCR/ABL1)2Dgt, Tg(BCR/ABL1)3Dgt, TRE-BCR-ABL, TRE-BCR/ABL, TRE-P10 BCR/ABL
Transgene:	Tg(tetO-BCR/ABL1)2Dgt Location: unknown

Transgene
origin

Strain of Origin:

FVB/N

Transgene
description

Transgene Type:	Transgenic (random, expressed)
Mutation:	Insertion
	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. (J:72377)

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:

Mouse Strains: 1 strain available Cell Lines: 0 lines available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	tg1	tg2
cellular			√
increased apoptosis			√
		tg1	tg2
digestive/alimentary system		√
abnormal small intestine morphology		√
		tg1	tg2
hematopoietic system		√	√
abnormal hematopoiesis		√
abnormal common myeloid progenitor cell morphology		√
increased leukocyte cell number		√	√
increased neutrophil cell number		√
abnormal lymphopoiesis		√
anemia			√
decreased platelet cell number			√
increased bone marrow cell number		√
increased hematopoietic stem cell number		√
increased megakaryocyte cell number		√
abnormal myeloblast morphology/development		√
abnormal spleen red pulp morphology		√
enlarged spleen		√	√
abnormal splenic cell ratio		√
		tg1	tg2
immune system		√	√
increased leukocyte cell number		√	√
increased neutrophil cell number		√
abnormal lymphopoiesis		√
abnormal spleen red pulp morphology		√
enlarged spleen		√	√
abnormal splenic cell ratio		√
abnormal lymph node morphology		√
enlarged lymph nodes			√
		tg1	tg2
life span/aging		√	√
premature death		√	√
		tg1	tg2
liver/biliary system		√
enlarged liver		√
		tg1	tg2
respiratory system		√
abnormal lung morphology		√
		tg1	tg2
skeleton			√
abnormal bone marrow morphology			√
		tg1	tg2
tumorigenesis		√	√
lymphoma		√
sarcoma		√
leukemia			√

		tg1	tg2
Disease Models		√
Leukemia, Chronic Myeloid; CML		√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype

Allelic Composition

Genetic Background

tg1 Disease Model

Tg(tetO-BCR/ABL1)2Dgt/0
Tg(Tal1-tTA)19Dgt/0

involves: C57BL/6 * DBA/2 * FVB/N

life span/agingpremature death (J:96511)

hematopoietic systemabnormal 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

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 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 hematopoietic stem cell number (J:96511)

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

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

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

enlarged spleen (J:96511)

after induction by withdrawal of tet treatment, splenomegaly invariably results

readministration of tet results in disappearance of palpable splenomegaly

abnormal splenic cell ratio (J:96511)

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

immune systemincreased 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 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

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

enlarged spleen (J:96511)

after induction by withdrawal of tet treatment, splenomegaly invariably results

readministration of tet results in disappearance of palpable splenomegaly

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 systemenlarged liver (J:96511)

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

respiratory systemabnormal lung morphology (J:96511)

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

digestive/alimentary systemabnormal small intestine morphology (J:96511)

infiltration of lamina propria by myeloid cells is observed

tumorigenesislymphoma (J:96511)

some mice develop lymphomas

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

sarcoma (J:96511)

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

Mouse Models of Human Disease	Note	Ref(s)
Models involving transgenes or other mutation types.¹
Leukemia, Chronic Myeloid; CML		J:96511

¹Models involving transgenes or other mutation types may also appear in other sections of the table.

tg2

Tg(tetO-BCR/ABL1)2Dgt/0
Tg(MMTVtTA)1Mam/0

involves: C57BL/6 * FVB/N * SJL

Disease
models

Mouse Models of Human Disease	Note	Genotype			Ref(s)
			Allelic Composition	Genetic Background
Models involving transgenes or other mutation types.¹
Leukemia, Chronic Myeloid; CML OMIM ID: 608232		tg1	Tg(tetO-BCR/ABL1)2Dgt/0 Tg(Tal1-tTA)19Dgt/0	involves: C57BL/6 * DBA/2 * FVB/N	J:96511

¹Models involving transgenes or other mutation types may also appear in other sections of the table.

Notes

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)

References

Original:	J:72377 Huettner CS et al., "Reversibility of acute B-cell leukaemia induced by BCR-ABL1." Nat Genet 2000 Jan;24(1):57-60
All:	4 reference(s)

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