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Phenotypes Associated with This Genotype
Genotype
MGI:6315197
Allelic
Composition
Tg(Vav1-Asxl1*Y588X)#Fcy/0
Genetic
Background
C57BL/6-Tg(Vav1-Asxl1*Y588X)#Fcy
Find Mice Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• moribund mice exhibit lower body weight

hematopoietic system
• hematopoietic stem cells/progenitor cells show skewed differentiation favoring monocytic/granulocytic lineage and toward myeloid lineage
• 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
• lower red blood cell counts in a portion of mice
• leukocytosis in 3 of 11 mice
• 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
• 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
• an increase in proportion of granulocyte/monocytic cells (Gr-1+/Mac-1+) is seen in peripheral blood, bone marrow, and spleens
• Howell-Jolly bodies in the erythrocytes in some mice
• some mice exhibit hyposegmented neutrophils with fine nuclear bridging and aberrant nuclear structure
• percentage of neutrophils is increased in most mice
• monocytosis in 2 of 11 mice with leukocytosis
• 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 in 7 of 11 mice, but in none of the mice with AML
• bone marrow shows a lower percentage of megakaryocyte-erythroid progenitor cells
• moribund mice show disorganized spleen architecture and higher frequencies of large/multinucleated megakaryocytes
• mice that develop myeloid leukemia, MPN, or MDS/MPN exhibit splenomegaly, with higher cellularity
• 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
• some mice exhibit hyposegmented neutrophils with fine nuclear bridging and aberrant nuclear structure
• percentage of neutrophils is increased in most mice
• lower red blood cell counts in a portion of mice
• leukocytosis in 3 of 11 mice
• monocytosis in 2 of 11 mice with leukocytosis
• moribund mice show disorganized spleen architecture and higher frequencies of large/multinucleated megakaryocytes
• mice that develop myeloid leukemia, MPN, or MDS/MPN exhibit splenomegaly, with higher cellularity

liver/biliary system
• mice that develop myeloid leukemia exhibit hepatosplenomegaly

mortality/aging
• shorter mean survival than wild-type mice

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


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
11/12/2019
MGI 6.14
The Jackson Laboratory