Tg(Tal1-tTA)19Dgt Transgene Detail MGI Mouse (MGI:3693328)

Tg(Tal1-tTA)19Dgt
Transgene Detail

Nomenclature

Symbol:	Tg(Tal1-tTA)19Dgt
Name:	transgene insertion 19, Daniel G Tenen
MGI ID:	MGI:3693328
Synonyms:	SCLtTA
Transgene:	Tg(Tal1-tTA)19Dgt Location: unknown

Transgene
origin

Strain of Origin:

(C57BL/6 x DBA/2)F1

Transgene
description

Transgene Type:	Transgenic (random, expressed)
Mutation:	Insertion
	The transgene consists of the SV40 minimal promoter, rabbit beta-globin intron 2, and the 3' enhancer sequence from the mouse T-cell acute lymphocytic leukemia gene driving expression of the tetracycline-regulated transactivator. (J:96511)

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
digestive/alimentary system		√
abnormal small intestine morphology		√
		tg1
hematopoietic system		√
abnormal hematopoiesis		√
abnormal common myeloid progenitor cell morphology		√
increased leukocyte cell number		√
increased neutrophil cell number		√
abnormal lymphopoiesis		√
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
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		√
		tg1
life span/aging		√
premature death		√
		tg1
liver/biliary system		√
enlarged liver		√
		tg1
respiratory system		√
abnormal lung morphology		√
		tg1
tumorigenesis		√
lymphoma		√
sarcoma		√

		tg1
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.

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.

References

Original:	J:96511 Koschmieder S et al., "Inducible chronic phase of myeloid leukemia with expansion of hematopoietic stem cells in a transgenic model of BCR-ABL leukemogenesis." Blood 2005 Jan 1;105(1):324-34
All:	1 reference(s)

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