Phenotypes Associated with This Genotype

Genotype
MGI:3693373

• Allelic Composition: Tg(tetO-BCR/ABL1)2Dgt/0; Tg(Tal1-tTA)19Dgt/0
• Genetic Background: involves: C57BL/6 * DBA/2 * FVB/N

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

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