Phenotypes associated with this allele

• Allele Symbol: Tg(Vav1-Asxl1*Y588X)#Fcy
• Allele Name: transgene insertion, Feng-Chun Yang
• Allele ID: MGI:6315194
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
tg1	Tg(Vav1-Asxl1*Y588X)#Fcy/0	C57BL/6-Tg(Vav1-Asxl1*Y588X)#Fcy	MGI:6315197

Genotype
MGI:6315197

tg1

• Allelic Composition: Tg(Vav1-Asxl1*Y588X)#Fcy/0
• Genetic Background: C57BL/6-Tg(Vav1-Asxl1*Y588X)#Fcy

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

growth/size/body

decreased body weight ( J:257690 )

• moribund mice exhibit lower body weight

enlarged spleen ( J:257690 )

• mice that develop myeloid leukemia, MPN, or MDS/MPN exhibit splenomegaly, with higher cellularity

hepatosplenomegaly ( J:257690 )

• mice that develop myeloid leukemia exhibit hepatosplenomegaly

hematopoietic system

abnormal definitive hematopoiesis ( J:257690 )

• hematopoietic stem cells/progenitor cells show skewed differentiation favoring monocytic/granulocytic lineage and toward myeloid lineage

increased megakaryocyte cell number ( J:257690 )

• bone marrow and spleen cell cytospins show increased numbers of multinucleated megakaryocytes

• mice exhibit a higher percentage of CD41+/CD61- megakaryocytic cells in the bone marrow and spleen

decreased leukocyte cell number ( J:257690 )

• lower red blood cell counts in a portion of mice

decreased lymphocyte cell number ( J:257690 )

increased leukocyte cell number ( J:257690 )

• leukocytosis in 3 of 11 mice

increased hematopoietic stem cell number ( J:257690 )

• bone marrow shows a higher percentage of Lin-Sca-1+cKit+ (LSK) cells, long-term HSCs (LSK/CD34-/FLK2-), short-term HSCs (LSK/CD34+/FLK2-), and granulocyte-macrophage progenitor cells and a lower percentage of megakaryocyte-erythroid progenitor cells, indicating a dysregulation of HSC/HPC pool and skewed differentiation toward myeloid lineage

abnormal myeloid cell morphology ( J:257690 )

• mice develop progressive myeloid malignancies mostly after 8 months of age, including acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS), and MDS/MPN

increased granulocyte monocyte progenitor cell number ( J:257690 )

• an increase in proportion of granulocyte/monocytic cells (Gr-1+/Mac-1+) is seen in peripheral blood, bone marrow, and spleens

decreased erythrocyte cell number ( J:257690 )

decreased hemoglobin content ( J:257690 )

increased number of Howell-Jolly bodies ( J:257690 )

• Howell-Jolly bodies in the erythrocytes in some mice

abnormal neutrophil morphology ( J:257690 )

• some mice exhibit hyposegmented neutrophils with fine nuclear bridging and aberrant nuclear structure

increased neutrophil cell number ( J:257690 )

• percentage of neutrophils is increased in most mice

increased monocyte cell number ( J:257690 )

• monocytosis in 2 of 11 mice with leukocytosis

increased myeloid cell number ( J:257690 )

• mice that develop MPN, MDS, or MDS/MPN exhibit liver and spleen with myeloid infiltration

• femurs of mice that develop MPN show an increased proportion of myeloid cells

thrombocytosis ( J:257690 )

• thrombocytosis in 7 of 11 mice, but in none of the mice with AML

decreased megakaryocyte-erythroid progenitor cell number ( J:257690 )

• bone marrow shows a lower percentage of megakaryocyte-erythroid progenitor cells

abnormal spleen morphology ( J:257690 )

• moribund mice show disorganized spleen architecture and higher frequencies of large/multinucleated megakaryocytes

enlarged spleen ( J:257690 )

• mice that develop myeloid leukemia, MPN, or MDS/MPN exhibit splenomegaly, with higher cellularity

hepatosplenomegaly ( J:257690 )

• mice that develop myeloid leukemia exhibit hepatosplenomegaly

abnormal hematopoietic stem cell physiology ( J:257690 )

• Lin-cKit+ (LK) cells have fewer Annexin V+/7-AAD- cells indicating less apoptosis

• the frequency of colony-forming unit cell (CFU-C) is higher in the bone marrow and bone marrow cells show higher replating capacity indicating increased HSC self-renewal capacity

immune system

abnormal neutrophil morphology ( J:257690 )

• some mice exhibit hyposegmented neutrophils with fine nuclear bridging and aberrant nuclear structure

increased neutrophil cell number ( J:257690 )

• percentage of neutrophils is increased in most mice

decreased leukocyte cell number ( J:257690 )

• lower red blood cell counts in a portion of mice

decreased lymphocyte cell number ( J:257690 )

increased leukocyte cell number ( J:257690 )

• leukocytosis in 3 of 11 mice

increased monocyte cell number ( J:257690 )

• monocytosis in 2 of 11 mice with leukocytosis

abnormal spleen morphology ( J:257690 )

• moribund mice show disorganized spleen architecture and higher frequencies of large/multinucleated megakaryocytes

enlarged spleen ( J:257690 )

• mice that develop myeloid leukemia, MPN, or MDS/MPN exhibit splenomegaly, with higher cellularity

hepatosplenomegaly ( J:257690 )

• mice that develop myeloid leukemia exhibit hepatosplenomegaly

mortality/aging

premature death ( J:257690 )

• shorter mean survival than wild-type mice

neoplasm

increased acute myeloid leukemia incidence ( J:257690 )

• seen in 27.3% of mice mostly after 8 months of age

increased myeloid sarcoma incidence ( J:257690 )

• intestinal myeloid sarcoma is seen in one leukemic mouse, with blast cell count being greater than 20%, and an increase in the proportion of myeloid cells and a decrease in erythroid islands

liver/biliary system

hepatosplenomegaly ( J:257690 )

• mice that develop myeloid leukemia exhibit hepatosplenomegaly

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acute myeloid leukemia		DOID:9119	OMIM:601626	J:257690
myelodysplastic syndrome		DOID:0050908	OMIM:614286	J:257690
myeloproliferative neoplasm		DOID:2226		J:257690