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Phenotypes Associated with This Genotype
Genotype
MGI:5565510
Allelic
Composition
Flt3tm2.1Dosm/Flt3+
Genetic
Background
B6.129(C)-Flt3tm2.1Dosm
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Flt3tm2.1Dosm mutation (0 available); any Flt3 mutation (52 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• detected at 12 weeks of age
• less severe than in B6.129(C)-Flt3tm1.1Dosm mice

mortality/aging
• median survival is 678 days, range of 394 to 826 days

hematopoietic system
• in a competitive repopulation assay transplanted cells engraft a higher levels compared to cells from wild-type or B6.129(C)-Flt3tm1.1Dosm mice
• increase in the number of colony forming unit-granulocyte/monocyte colonies formed by cultured bone marrow cells at 12 weeks of age
• most mice (18 of 24) develop a myeloproliferative neoplastic phenotype that is less aggressive than in B6.129(C)-Flt3tm1.1Dosm mice
• seen in varying degrees in mice with a myeloproliferative neoplastic phenotype
• increase in the fractions of c-Kit+ Sca-1+ Lin- (KSL) and multipotent progenitor (Lin-c-Kit+Sca-1+CD135+CD34+) cells in the bone marrow
• about a 3 fold increase in the frequency of long term hematopoietic stem cells (LT-HSC) compared to wild-type and B6.129(C)-Flt3tm1.1Dosm mice
• however, the fraction of c-Kit+ Sca-1+ Lin-(KSL)-signaling lymphocyte activation molecule (KSL-SLAM) cells is similar to wild-type controls
• 2 of 3 mice with histiocytic sarcoma show an increase in megakaryocytes that form clusters in the bone marrow and spleen
• 2 of 3 mice with histiocytic sarcoma show marked thrombocytosis in the peripheral blood
• mild increase in peripheral WBC counts
• some mice that develop a myeloproliferative neoplastic phenotype (10 of 18) also have extranodal B cell masses
• these masses are frequently adherent to or involve the gut and/or are located in the chest cavity
• expansion of pre-pro B and pro B cells
• level of architecture disruption and cellular expansion is less than in B6.129(C)-Flt3tm1.1Dosm mice at 3 and 12 months of age
• detected at 12 weeks of age
• less severe than in B6.129(C)-Flt3tm1.1Dosm mice
• myeloid infiltrate in the red pulp in mice with a myeloproliferative neoplastic phenotype
• in many mice with a myeloproliferative neoplastic phenotype
• treatment with Lestaurtinib, but not Sorafenib, decreases bone marrow cell proliferation

skeleton
• increase in the fractions of c-Kit+ Sca-1+ Lin- (KSL) and multipotent progenitor (Lin-c-Kit+Sca-1+CD135+CD34+) cells in the bone marrow
• about a 3 fold increase in the frequency of long term hematopoietic stem cells (LT-HSC) compared to wild-type and B6.129(C)-Flt3tm1.1Dosm mice
• however, the fraction of c-Kit+ Sca-1+ Lin-(KSL)-signaling lymphocyte activation molecule (KSL-SLAM) cells is similar to wild-type controls

neoplasm
• a T cell rich, B cell lymphoma is seen in 1 mouse
• 3 mice display histiocytic sarcoma with bone marrow and splenic involvement
• splenic hemangiosarcoma is seen in 2 of 24 mice, with one of these showing concurrent B cell expansion in the spleen

immune system
• increase in the number of colony forming unit-granulocyte/monocyte colonies formed by cultured bone marrow cells at 12 weeks of age
• most mice (18 of 24) develop a myeloproliferative neoplastic phenotype that is less aggressive than in B6.129(C)-Flt3tm1.1Dosm mice
• mild increase in peripheral WBC counts
• some mice that develop a myeloproliferative neoplastic phenotype (10 of 18) also have extranodal B cell masses
• these masses are frequently adherent to or involve the gut and/or are located in the chest cavity
• expansion of pre-pro B and pro B cells
• level of architecture disruption and cellular expansion is less than in B6.129(C)-Flt3tm1.1Dosm mice at 3 and 12 months of age
• detected at 12 weeks of age
• less severe than in B6.129(C)-Flt3tm1.1Dosm mice
• myeloid infiltrate in the red pulp in mice with a myeloproliferative neoplastic phenotype
• in many mice with a myeloproliferative neoplastic phenotype

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
acute myeloid leukemia DOID:9119 OMIM:601626
J:205200


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
09/13/2022
MGI 6.21
The Jackson Laboratory