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

• ♀: 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