Phenotypes associated with this allele

• Allele Symbol: Tg(CTSG-RARA/ZBTB16)#Ppp
• Allele Name: transgene insertion, Pier Paolo Pandolfi
• Allele ID: MGI:3527936
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Tg(CTSG-RARA/ZBTB16)#Ppp/0 Tg(CTSG-ZBTB16/RARA)#Ppp/0	Not Specified	MGI:5514339
tg2	Tg(CTSG-RARA/ZBTB16)#Ppp/0	Not Specified	MGI:5514279

Genotype
MGI:5514339

cx1

• Allelic Composition: Tg(CTSG-RARA/ZBTB16)#Ppp/0; Tg(CTSG-ZBTB16/RARA)#Ppp/0
• Genetic Background: Not Specified

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

cellular

decreased apoptosis ( J:65878 )

• overall rate of bone marrow cell apoptosis and growth factor deprivation-induced programmed cell death is reduced

hematopoietic system

abnormal definitive hematopoiesis ( J:65878 )

• clonogenic capacity of hematopoietic precursors is reduced, with a reduced number of colony-forming unit-granulocyte, macrophage (CFU-GM)

abnormal myelopoiesis ( J:65878 )

• leukemia is preceded by a myeloproliferative disorder characterized by the accumulation of immature myeloid cells and promyelocytes in the bone marrow and spleen, indicating impaired myeloid differentiation

anemia ( J:65878 )

thrombocytopenia ( J:65878 )

• low platelet counts in the peripheral blood

increased leukocyte cell number ( J:65878 )

• mild increase in white blood cell counts in the peripheral blood

• leukocytosis is much less pronounced than in single Tg(CTSG-ZBTB16/RARA)#Ppp mutants

abnormal bone marrow cell physiology ( J:65878 )

• proliferation rate of bone marrow cells is higher

• the number of leukemic clusters (small colonies of 8-20 cells) observed in bone marrow is increased compared to wild-type bone marrow

• overall rate of bone marrow cell apoptosis and growth factor deprivation-induced programmed cell death is reduced

immune system

abnormal myelopoiesis ( J:65878 )

• leukemia is preceded by a myeloproliferative disorder characterized by the accumulation of immature myeloid cells and promyelocytes in the bone marrow and spleen, indicating impaired myeloid differentiation

increased leukocyte cell number ( J:65878 )

• mild increase in white blood cell counts in the peripheral blood

• leukocytosis is much less pronounced than in single Tg(CTSG-ZBTB16/RARA)#Ppp mutants

neoplasm

increased leukemia incidence ( J:65878 )

• 100% penetrance of leukemia after 6 months of age

• leukemias are unresponsive to retinoic acid and survival following treatment is shorter (30 days) than in untreated mutants (4 weeks from diagnosis)

• retinoic acid-induced differentiation in leukemic cells is reduced compared to single single Tg(CTSG-ZBTB16/RARA)#Ppp mutants

increased acute promyelocytic leukemia incidence ( J:65878 )

• leukemia is characterized by an accumulation of immature blasts and of cells blocked at the promyelocytic stage of differentiation (more than 50% of promyelocytes in bone marrow in some cases)

• leukemia is also characterized by a significant accumulation of c-Kit+/CD34+ and Gr-1+/Mac-1- cells representing early myeloid progenitors in the bone marrow and spleen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acute promyelocytic leukemia		DOID:0060318	OMIM:612376	J:65878

Genotype
MGI:5514279

tg2

• Allelic Composition: Tg(CTSG-RARA/ZBTB16)#Ppp/0
• Genetic Background: Not Specified

cellular

decreased apoptosis ( J:65878 )

• overall rate of bone marrow cell apoptosis and growth factor deprivation-induced programmed cell death is reduced

hematopoietic system

enlarged spleen ( J:65878 )

• approximately 20% of mutants develop splenomegaly after the first year of life

abnormal myelopoiesis ( J:65878 )

• perturbed myelopoiesis, with slow and progressive accumulation of myeloid cells in the bone marrow and spleen; these cells retain the ability to terminally differentiate into mature granulocytes

myeloid hyperplasia ( J:65878 )

• progressive hyperplasia of the myeloid/granulocytic compartment in the bone marrow

thrombocytopenia ( J:65878 )

• low platelet counts in the peripheral blood

immune system

enlarged spleen ( J:65878 )

• approximately 20% of mutants develop splenomegaly after the first year of life

abnormal myelopoiesis ( J:65878 )

• perturbed myelopoiesis, with slow and progressive accumulation of myeloid cells in the bone marrow and spleen; these cells retain the ability to terminally differentiate into mature granulocytes

myeloid hyperplasia ( J:65878 )

• progressive hyperplasia of the myeloid/granulocytic compartment in the bone marrow

neoplasm

neoplasm ( J:65878 )

N • mutants do not develop leukemia

growth/size/body

enlarged spleen ( J:65878 )

• approximately 20% of mutants develop splenomegaly after the first year of life