Phenotypes Associated with This Genotype

Genotype
MGI:5565510

• Allelic Composition: Flt3^tm2.1Dosm/Flt3⁺
• Genetic Background: B6.129(C)-Flt3^tm2.1Dosm

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

mortality/aging

premature death ( J:205200 )

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

hematopoietic system

abnormal definitive hematopoiesis ( J:205200 )

• in a competitive repopulation assay transplanted cells engraft a higher levels compared to cells from wild-type or B6.129(C)-Flt3^tm1.1Dosm mice

abnormal myelopoiesis ( J:205200 )

• increase in the number of colony forming unit-granulocyte/monocyte colonies formed by cultured bone marrow cells at 12 weeks of age

myeloid hyperplasia ( J:205200 )

• most mice (18 of 24) develop a myeloproliferative neoplastic phenotype that is less aggressive than in B6.129(C)-Flt3^tm1.1Dosm mice

extramedullary hematopoiesis ( J:205200 )

• seen in varying degrees in mice with a myeloproliferative neoplastic phenotype

increased bone marrow cell number ( J:205200 )

• 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)-Flt3^tm1.1Dosm mice

• however, the fraction of c-Kit+ Sca-1+ Lin-(KSL)-signaling lymphocyte activation molecule (KSL-SLAM) cells is similar to wild-type controls

increased megakaryocyte cell number ( J:205200 )

• 2 of 3 mice with histiocytic sarcoma show an increase in megakaryocytes that form clusters in the bone marrow and spleen

thrombocytosis ( J:205200 )

• 2 of 3 mice with histiocytic sarcoma show marked thrombocytosis in the peripheral blood

increased leukocyte cell number ( J:205200 )

• mild increase in peripheral WBC counts

abnormal B cell morphology ( J:205200 )

• 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

increased pro-B cell number ( J:205200 )

• expansion of pre-pro B and pro B cells

increased pre-pro B cell number ( J:205200 )

abnormal spleen morphology ( J:205200 )

• level of architecture disruption and cellular expansion is less than in B6.129(C)-Flt3^tm1.1Dosm mice at 3 and 12 months of age

enlarged spleen ( J:205200 )

• detected at 12 weeks of age

• less severe than in B6.129(C)-Flt3^tm1.1Dosm mice

intermingled spleen red and white pulp ( J:205200 )

• myeloid infiltrate in the red pulp in mice with a myeloproliferative neoplastic phenotype

increased spleen white pulp amount ( J:205200 )

• in many mice with a myeloproliferative neoplastic phenotype

abnormal bone marrow cell physiology ( J:205200 )

• treatment with Lestaurtinib, but not Sorafenib, decreases bone marrow cell proliferation

skeleton

abnormal bone marrow morphology ( J:205200 )

• 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)-Flt3^tm1.1Dosm 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

increased B cell derived lymphoma incidence ( J:205200 )

• a T cell rich, B cell lymphoma is seen in 1 mouse

increased histiocytic sarcoma incidence ( J:205200 )

• 3 mice display histiocytic sarcoma with bone marrow and splenic involvement

increased hemangiosarcoma incidence ( J:205200 )

• splenic hemangiosarcoma is seen in 2 of 24 mice, with one of these showing concurrent B cell expansion in the spleen

immune system

abnormal myelopoiesis ( J:205200 )

• increase in the number of colony forming unit-granulocyte/monocyte colonies formed by cultured bone marrow cells at 12 weeks of age

myeloid hyperplasia ( J:205200 )

• most mice (18 of 24) develop a myeloproliferative neoplastic phenotype that is less aggressive than in B6.129(C)-Flt3^tm1.1Dosm mice

increased leukocyte cell number ( J:205200 )

• mild increase in peripheral WBC counts

abnormal B cell morphology ( J:205200 )

• 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

increased pro-B cell number ( J:205200 )

• expansion of pre-pro B and pro B cells

increased pre-pro B cell number ( J:205200 )

abnormal spleen morphology ( J:205200 )

• level of architecture disruption and cellular expansion is less than in B6.129(C)-Flt3^tm1.1Dosm mice at 3 and 12 months of age

enlarged spleen ( J:205200 )

• detected at 12 weeks of age

• less severe than in B6.129(C)-Flt3^tm1.1Dosm mice

intermingled spleen red and white pulp ( J:205200 )

• myeloid infiltrate in the red pulp in mice with a myeloproliferative neoplastic phenotype

increased spleen white pulp amount ( J:205200 )

• in many mice with a myeloproliferative neoplastic phenotype

growth/size/body

enlarged spleen ( J:205200 )

• detected at 12 weeks of age

• less severe than in B6.129(C)-Flt3^tm1.1Dosm mice

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