Mouse Genome Informatics
cx1
    Tg(CTSG-ZBTB16/RARA)#Ppp/0
Zbtb16tm1Ppp/Zbtb16tm1Ppp

involves: 129S1/Sv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 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
OMIM IDRef(s)
Acute Promyelocytic Leukemia; APL 612376 J:65878


Mouse Genome Informatics
cx2
    Tg(CTSG-RARA/ZBTB16)#Ppp/0
Tg(CTSG-ZBTB16/RARA)#Ppp/0

Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• overall rate of bone marrow cell apoptosis and growth factor deprivation-induced programmed cell death is reduced

hematopoietic system
• clonogenic capacity of hematopoietic precursors is reduced, with a reduced number of colony-forming unit-granulocyte, macrophage (CFU-GM)
• 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
• low platelet counts in the peripheral blood
• 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
• 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
• 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
• 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

tumorigenesis
• 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
• 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
OMIM IDRef(s)
Acute Promyelocytic Leukemia; APL 612376 J:65878


Mouse Genome Informatics
tg3
    Tg(CTSG-ZBTB16/RARA)#Ppp/0
Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• 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

immune system
• 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

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

tumorigenesis
• 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
• 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)