Phenotypes associated with this allele

• Allele Symbol: Tg(CTSG-ZBTB16/RARA)#Ppp
• Allele Name: transgene insertion, Pier Paolo Pandolfi
• Allele ID: MGI:3527937
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Tg(CTSG-ZBTB16/RARA)#Ppp/0 Zbtb16^tm1Ppp/Zbtb16^tm1Ppp	involves: 129S1/Sv	MGI:5514344
cx2	Tg(CTSG-RARA/ZBTB16)#Ppp/0 Tg(CTSG-ZBTB16/RARA)#Ppp/0	Not Specified	MGI:5514339
tg3	Tg(CTSG-ZBTB16/RARA)#Ppp/0	Not Specified	MGI:5514273

Genotype
MGI:5514344

cx1

• Allelic Composition: Tg(CTSG-ZBTB16/RARA)#Ppp/0; Zbtb16^tm1Ppp/Zbtb16^tm1Ppp
• Genetic Background: involves: 129S1/Sv

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

neoplasm

increased acute promyelocytic leukemia incidence ( J:65878 )

• develop leukemia after 6 months of age characterized by an accumulation of blast/promyelocytic cells in the bone marrow and spleen in the absence of leukocytosis resembling acute promyelocytic leukemia

• leukemia is also characterized by infiltrating cells that are c-Kit, Gr-1, Mac-1 positive and display promyelocytic features

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

Genotype
MGI:5514339

cx2

• Allelic Composition: Tg(CTSG-RARA/ZBTB16)#Ppp/0; Tg(CTSG-ZBTB16/RARA)#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

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:5514273

tg3

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

hematopoietic system

abnormal myelopoiesis ( J:78201 )

• leukemia is preceded by a myeloproliferative disorder of variable duration characterized by progressive accumulation of myeloid precursors in the bone marrow and spleen, and in some cases the peripheral blood

increased leukocyte cell number ( J:65878 , J:78201 )

immune system

abnormal myelopoiesis ( J:78201 )

• leukemia is preceded by a myeloproliferative disorder of variable duration characterized by progressive accumulation of myeloid precursors in the bone marrow and spleen, and in some cases the peripheral blood

increased leukocyte cell number ( J:65878 , J:78201 )

mortality/aging

premature death ( J:78201 )

• all mice die of leukemia between 6 months and 1.5 years of age

neoplasm

increased leukemia incidence ( J:78201 )

• all mice develop leukemia

• leukemia is resistant to retinoic acid treatment and complete remission is not observed, although survival is prolonged and hematopoietic differentiation is induced

• however, much higher doses than normal of retinoic acid treatment leads to remission

increased chronic myelocytic leukemia incidence ( J:65878 , J:78201 )

• leukemia is characterized by leukocytosis in peripheral blood and infiltration in all organs by myeloid leukemic progenitors with promyelocityic and myelocytic features that retain the capacity to terminally mature, resembling chronic myeloid leukemia (J:78201)