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Phenotypes Associated with This Genotype
Genotype
MGI:5514339
Allelic
Composition
Tg(CTSG-RARA/ZBTB16)#Ppp/0
Tg(CTSG-ZBTB16/RARA)#Ppp/0
Genetic
Background
Not Specified
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phenotype observed in females
phenotype observed in males
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)
• 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
• low platelet counts in the peripheral blood
• 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
• 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
• 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
• 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

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 ID Ref(s)
Acute Promyelocytic Leukemia; APL 612376 J:65878


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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
04/19/2016
MGI 6.03
The Jackson Laboratory