Phenotypes Associated with This Genotype

Genotype
MGI:3620520

• Allelic Composition: Tg(CTSG-PML/RARA)135Ley/0; Tg(CTSG-RARA/PML)#Ley/0
• Genetic Background: involves: C3H * C57BL/6

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

hematopoietic system

enlarged spleen ( J:59080 )

• spleens of young (< 8 mo), pre-leukemic doubly transgenic mice are significantly enlarged

anemia ( J:59080 )

• peripheral blood hemoglobin concentrations are similarly reduced in Tg(CTSG-PML/RARA)135Ley and in doubly transgenic mice with leukemia

thrombocytopenia ( J:59080 )

• platelet counts are similarly diminished in Tg(CTSG-PML/RARA)135Ley and in doubly transgenic mice with leukemia

increased leukocyte cell number ( J:59080 )

• peripheral blood WBC counts are similarly elevated in Tg(CTSG-PML/RARA)135Ley and in doubly transgenic mice with leukemia, with high proportions of early myeloid-lineage cells

abnormal spleen red pulp morphology ( J:59080 )

• young (< 8 mo), pre-leukemic doubly transgenic mice have elevated numbers of early myeloid cells in the red pulp of the spleen

neoplasm

increased acute promyelocytic leukemia incidence ( J:59080 )

• 7 of 36 (19.4%) and 16 of 28 (57%) doubly transgenic mice of independent cohorts developed acute premyelocytic leukemia (APML) by 12 and 24 months of age, respectively

• the average latencies to onset of APML in two cohorts of doubly transgenic mice were 9.7 +/- 5.2 months and 12.7 +/- 3.3 months

• the proportions of early myeloid-lineage cells is similarly elevated in peripheral blood of Tg(CTSG-PML/RARA)135Ley and of doubly transgenic mice with leukemia

• an abnormal population of Gr-1⁺ CD34⁺ cells is present in bone marrow and blood of doubly transgenic mice, as of Tg(CTSG-PML/RARA)135Ley mice, with leukemia and accounts for a large proportion of leukemic spleen cells (55 +/- 13%; N=16; range 28-67%); histologic examination shows this population is enriched for immature myeloid cells

• culture of spleen cells from doubly transgenic mice with leukemia in the presence of all trans retinoic acid (ATRA) induces their differentiation to a similar extent as of splenocytes from leukemic Tg(CTSG-PML/RARA)135Ley mice

immune system

immune system phenotype ( J:59080 )

N • Gr-1⁺ cells from Tg(CTSG-PML/RARA)135Ley and doubly transgenic mice with leukemia exhibit surface expression of MHC class I markers at levels similar to that of wild-type Gr-1⁺ spleen cells

enlarged spleen ( J:59080 )

• spleens of young (< 8 mo), pre-leukemic doubly transgenic mice are significantly enlarged

increased leukocyte cell number ( J:59080 )

• peripheral blood WBC counts are similarly elevated in Tg(CTSG-PML/RARA)135Ley and in doubly transgenic mice with leukemia, with high proportions of early myeloid-lineage cells

abnormal spleen red pulp morphology ( J:59080 )

• young (< 8 mo), pre-leukemic doubly transgenic mice have elevated numbers of early myeloid cells in the red pulp of the spleen

growth/size/body

enlarged spleen ( J:59080 )

• spleens of young (< 8 mo), pre-leukemic doubly transgenic mice are significantly enlarged