All Phenotypes Flt3<+> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Flt3^tm1.1Dosm/Flt3⁺	B6.129(C)-Flt3^tm1.1Dosm	MGI:5565512
ht2	Flt3^tm2.1Dosm/Flt3⁺	B6.129(C)-Flt3^tm2.1Dosm	MGI:5565510
ht3	Flt3^tm1Dgg/Flt3⁺	involves: 129S1/Sv * 129X1/SvJ * BALB/c	MGI:3763427
ht4	Flt3^tm1Dgg/Flt3⁺	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3763425
cn5	Flt3^tm1Dosm/Flt3⁺ Tg(Mx1-cre)1Cgn/0	B6.Cg-Flt3^tm1Dosm Tg(Mx1-cre)1Cgn	MGI:3819966
cx6	Flt3^tm1Dgg/Flt3⁺ Kmt2a^tm1Clgr/Kmt2a⁺	involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6J	MGI:5445344

Allelic Composition	Flt3^tm1.1Dosm/Flt3⁺
Genetic Background	B6.129(C)-Flt3^tm1.1Dosm

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Flt3^tm1.1Dosm mutation (0 available); any Flt3 mutation (94 available)

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

mortality/aging

premature death ( J:205200 )

• median survival is 430 days

hematopoietic system

abnormal definitive hematopoiesis ( J:205200 )

• impaired ability to engraft in a competitive repopulation assay

arrested B cell differentiation ( J:205200 )

• severe block in B cell development with few cells progressing past the early pro-B cell stage

abnormal bone marrow cell number ( J:205200 )

• normal architecture is largely replaced by myeloid progenitors in mice at 3 and 12 months of age

decreased bone marrow cell number ( J:205200 )

• decrease in the fraction of functional c-Kit+ Sca-1+ Lin-(KSL)-signaling lymphocyte activation molecule (KSL-SLAM) cells

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

abnormal spleen morphology ( J:205200 )

• architecture disruption and cellular expansion at 3 and 12 months of age

enlarged spleen ( J:205200 )

• detected at 12 weeks of age

increased spleen white pulp amount ( J:205200 )

abnormal bone marrow cell physiology ( J:205200 )

• treatment with either Lestaurtinib or Sorafenib decreases bone marrow cell proliferation

skeleton

abnormal bone marrow morphology ( J:205200 )

• architecture disruption and cellular expansion at 3 and 12 months of age

• normal architecture is largely replaced by myeloid progenitors in mice at 3 and 12 months of age

immune system

arrested B cell differentiation ( J:205200 )

• severe block in B cell development with few cells progressing past the early pro-B cell stage

abnormal spleen morphology ( J:205200 )

• architecture disruption and cellular expansion at 3 and 12 months of age

enlarged spleen ( J:205200 )

• detected at 12 weeks of age

increased spleen white pulp amount ( J:205200 )

growth/size/body

enlarged spleen ( J:205200 )

• detected at 12 weeks of age

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

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

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Flt3^tm2.1Dosm mutation (0 available); any Flt3 mutation (94 available)

♀	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

Allelic Composition	Flt3^tm1Dgg/Flt3⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * BALB/c

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Flt3^tm1Dgg mutation (8 available); any Flt3 mutation (94 available)

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

hematopoietic system

abnormal hematopoietic system morphology/development ( J:126003 )

• authors state that mice display the same phenotype as when they are on a background containing C57BL/6

Allelic Composition	Flt3^tm1Dgg/Flt3⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Flt3^tm1Dgg mutation (8 available); any Flt3 mutation (94 available)

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

hematopoietic system

enlarged spleen ( J:126003 )

• mice develop a variable and progressive splenomegaly that is not as severe as in homozygous mice

abnormal definitive hematopoiesis ( J:126003 )

• bone marrow cells exhibit a two-fold increase in the Lin-Sca1+cKit+ (LSK) compartment compared to in wild-type mice

• fewer LSK cells undergo apoptosis compared to in wild-type

• monocytes are present in the bone marrow and liver in a background of increased number of maturing myeloid cells is increased compared to in wild-type mice

abnormal B cell differentiation ( J:126003 )

• B cell maturation is blocked at the pre-B stage

decreased B cell number ( J:126003 )

• the rise in monocytes in the bone marrow and spleen is accompanied by a decrease in the percentage of T and B lymphoid cells

decreased mature B cell number ( J:126003 )

• the number of mature B cells in the bone marrow and spleen is decreased compared to in wild-type mice

decreased T cell number ( J:126003 )

• the rise in monocytes in the bone marrow and spleen is accompanied by a decrease in the percentage of T and B lymphoid cells

increased leukocyte cell number ( J:126003 )

• mice exhibit leukocytosis and monocytosis with a reversal in the neutrophil to lymphocyte ratio compared to in wild-type mice

increased granulocyte number ( J:126003 )

• granulocyte populations are increased in peripheral blood compared to in wild-type mice

increased monocyte cell number ( J:126003 )

• monocyte populations are increased in peripheral blood

• monocytes are present in the bone marrow and liver in a background of increased number of maturing myeloid cells is increased compared to in wild-type mice

increased spleen red pulp amount ( J:126003 )

• expanded red pulp is comprised of mainly mature myeloid and ad-mixed erythroid elements

increased spleen white pulp amount ( J:126003 )

• expanded white pulp is comprised of cells resembling maturing monocytes

immune system

enlarged spleen ( J:126003 )

• mice develop a variable and progressive splenomegaly that is not as severe as in homozygous mice

abnormal B cell differentiation ( J:126003 )

• B cell maturation is blocked at the pre-B stage

decreased B cell number ( J:126003 )

• the rise in monocytes in the bone marrow and spleen is accompanied by a decrease in the percentage of T and B lymphoid cells

decreased mature B cell number ( J:126003 )

• the number of mature B cells in the bone marrow and spleen is decreased compared to in wild-type mice

decreased T cell number ( J:126003 )

• the rise in monocytes in the bone marrow and spleen is accompanied by a decrease in the percentage of T and B lymphoid cells

increased leukocyte cell number ( J:126003 )

• mice exhibit leukocytosis and monocytosis with a reversal in the neutrophil to lymphocyte ratio compared to in wild-type mice

increased granulocyte number ( J:126003 )

• granulocyte populations are increased in peripheral blood compared to in wild-type mice

increased monocyte cell number ( J:126003 )

• monocyte populations are increased in peripheral blood

• monocytes are present in the bone marrow and liver in a background of increased number of maturing myeloid cells is increased compared to in wild-type mice

increased spleen red pulp amount ( J:126003 )

• expanded red pulp is comprised of mainly mature myeloid and ad-mixed erythroid elements

increased spleen white pulp amount ( J:126003 )

• expanded white pulp is comprised of cells resembling maturing monocytes

growth/size/body

enlarged spleen ( J:126003 )

• mice develop a variable and progressive splenomegaly that is not as severe as in homozygous mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
juvenile myelomonocytic leukemia		DOID:0050458	OMIM:607785	J:126003

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

mortality/aging

premature death ( J:133528 )

• PIPC treated-mice die between 6 and 20 months of age with a median survival time of 10 months

hematopoietic system

enlarged spleen ( J:133528 )

• spleen size in PIPC treated-mice is 2.5-fold greater than normal at 2 months of age and 5-fold greater at 12 months of age

abnormal definitive hematopoiesis ( J:133528 )

• bone marrow and spleen cells of PIPC treated-mice produce more colony forming units-granulocyte/monocyte (CFU-GM) than in wild-type cultures

• however, the number of burst-forming units-erythroid is normal

• cultured bone marrow and spleen cells of PIPC treated-mice produce more immature cells than wild-type cultures

• transplanted bone marrow cells of PIPC treated-mice are capable of producing bone marrow hypercellularity and splenomegaly in recipients

increased pro-B cell number ( J:133528 )

• in PIPC treated-mice

arrested B cell differentiation ( J:133528 )

• B cell maturation in PIPC treated-mice is blocked resulting in decreased pre-B cells and increased pro-B cells compared to in wild-type mice

extramedullary hematopoiesis ( J:133528 )

• in some older PIPC treated-mice

abnormal bone marrow cell morphology/development ( J:133528 )

• bone marrow and spleen cells of PIPC treated-mice produce more colony forming units-granulocyte/monocyte (CFU-GM) in culture compared to wild-type cells

• however, the number of burst-forming units-erythroid is normal

• cultured bone marrow and spleen cells of PIPC treated-mice produce more immature cells than wild-type cultures

increased bone marrow cell number ( J:133528 )

• at 12 months, bone marrow of PIPC treated-mice becomes hypercellular with accumulation of immature myeloid cells and increased mononuclear cell numbers unlike in wild-type mice

• the fraction of undifferentiated or partially differentiated myeloid cells in PIPC treated-mice is increased compared to in wild-type mice

decreased megakaryocyte cell number ( J:133528 )

• at 2 months, megakaryocyte populations in the bone marrow of PIPC treated-mice are reduced compared to in wild-type mice

decreased erythrocyte cell number ( J:133528 )

• at 2 months, erythrocyte populations in the bone marrow of PIPC treated-mice are reduced compared to in wild-type mice

• at 12 months, PIPC treated-mice mice exhibit a decrease in the number of Ter119 cells in the bone marrow

decreased hemoglobin content ( J:133528 )

• at 12 months of age but not 2 months of age in PIPC treated-mice

increased dendritic cell number ( J:133528 )

• in the bone marrow and spleen in PIPC treated-mice

decreased leukocyte cell number ( J:133528 )

• slightly at 2 months of age in PIPC treated-mice

decreased neutrophil cell number ( J:133528 )

• slightly at 2 months of age in PIPC treated-mice

decreased lymphocyte cell number ( J:133528 )

• slightly at 2 months of age in PIPC treated-mice

decreased B cell number ( J:133528 )

• B lymphoid populations in the spleen are reduced compared to in wild-type mice

• at 2 months and 12 months of age, B lymphoid populations in the bone marrow of PIPC treated-mice are reduced compared to in wild-type mice

decreased pre-B cell number ( J:133528 )

• in the bone marrow at 12 months of age in PIPC treated-mice

increased leukocyte cell number ( J:133528 )

• at 12 months of age in PIPC treated-mice

increased granulocyte number ( J:133528 )

• granulocyte and monocyte populations of PIPC treated-mice are expanded in the spleen compared to in wild-type mice

• at 2 months, granulocyte populations in the bone marrow of PIPC treated-mice are expanded compared to in wild-type mice

• at 12 months, the bone marrow of PIPC treated-mice contains more Gr-1 cells than in wild-type mice

increased neutrophil cell number ( J:133528 )

• at 12 months of age in PIPC treated-mice

increased monocyte cell number ( J:133528 )

• granulocyte and monocyte populations from PIPC treated-mice are expanded in the spleen compared to in wild-type mice

• at 2 months, monocyte populations in the bone marrow of PIPC treated-mice are expanded compared to in wild-type mice

• at 12 months, the bone marrow of PIPC treated-mice contains more Mac-1 cells than in wild-type mice

increased hematopoietic stem cell number ( J:133528 )

• the number of Lin^-/low and/or c-KIT+ cells in the bone marrow of PIPC treated-mice is increased at 2 months of age, and even more so at 12 months of age, compared to in wild-type mice

abnormal spleen white pulp morphology ( J:133528 )

• white pulp in PIPC treated-mice contains more immature myeloid less and fewer mature lymphocytes than in wild-type mice

intermingled spleen red and white pulp ( J:133528 )

• at 2 months, areas of myeloproliferation in PIPC treated-mice are found within the red pulp unlike in wild-type mice

• at 12 months, PIPC treated-mice mice exhibit progressive myeloproliferation with expansion mostly of immature myeloid cells in the red pulp unlike in wild-type mice

cellular

delayed cellular replicative senescence ( J:133528 )

• bone marrow cells of PIPC treated-mice can be cultured for longer than wild-type cells without immortalization and with reduced requirement of cytokines

immune system

enlarged spleen ( J:133528 )

• spleen size in PIPC treated-mice is 2.5-fold greater than normal at 2 months of age and 5-fold greater at 12 months of age

increased pro-B cell number ( J:133528 )

• in PIPC treated-mice

arrested B cell differentiation ( J:133528 )

• B cell maturation in PIPC treated-mice is blocked resulting in decreased pre-B cells and increased pro-B cells compared to in wild-type mice

increased dendritic cell number ( J:133528 )

• in the bone marrow and spleen in PIPC treated-mice

decreased leukocyte cell number ( J:133528 )

• slightly at 2 months of age in PIPC treated-mice

decreased neutrophil cell number ( J:133528 )

• slightly at 2 months of age in PIPC treated-mice

decreased lymphocyte cell number ( J:133528 )

• slightly at 2 months of age in PIPC treated-mice

decreased B cell number ( J:133528 )

• B lymphoid populations in the spleen are reduced compared to in wild-type mice

• at 2 months and 12 months of age, B lymphoid populations in the bone marrow of PIPC treated-mice are reduced compared to in wild-type mice

decreased pre-B cell number ( J:133528 )

• in the bone marrow at 12 months of age in PIPC treated-mice

increased leukocyte cell number ( J:133528 )

• at 12 months of age in PIPC treated-mice

increased granulocyte number ( J:133528 )

• granulocyte and monocyte populations of PIPC treated-mice are expanded in the spleen compared to in wild-type mice

• at 2 months, granulocyte populations in the bone marrow of PIPC treated-mice are expanded compared to in wild-type mice

• at 12 months, the bone marrow of PIPC treated-mice contains more Gr-1 cells than in wild-type mice

increased neutrophil cell number ( J:133528 )

• at 12 months of age in PIPC treated-mice

increased monocyte cell number ( J:133528 )

• granulocyte and monocyte populations from PIPC treated-mice are expanded in the spleen compared to in wild-type mice

• at 2 months, monocyte populations in the bone marrow of PIPC treated-mice are expanded compared to in wild-type mice

• at 12 months, the bone marrow of PIPC treated-mice contains more Mac-1 cells than in wild-type mice

abnormal spleen white pulp morphology ( J:133528 )

• white pulp in PIPC treated-mice contains more immature myeloid less and fewer mature lymphocytes than in wild-type mice

intermingled spleen red and white pulp ( J:133528 )

• at 2 months, areas of myeloproliferation in PIPC treated-mice are found within the red pulp unlike in wild-type mice

• at 12 months, PIPC treated-mice mice exhibit progressive myeloproliferation with expansion mostly of immature myeloid cells in the red pulp unlike in wild-type mice

growth/size/body

enlarged spleen ( J:133528 )

• spleen size in PIPC treated-mice is 2.5-fold greater than normal at 2 months of age and 5-fold greater at 12 months of age

Allelic Composition	Flt3^tm1Dgg/Flt3⁺ Kmt2a^tm1Clgr/Kmt2a⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Flt3^tm1Dgg mutation (8 available); any Flt3 mutation (94 available)
Kmt2a^tm1Clgr mutation (0 available); any Kmt2a mutation (137 available)

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

mortality/aging

premature death ( J:189096 )

• median survival of 49 weeks of age compared to 75-94 weeks of age for wild-type and single heterozygotes

neoplasm

increased leukemia incidence ( J:189096 )

• 100% penetrance of acute leukemia at a median age of 49 weeks

• 70% develop acute myeloid leukemia

• 12% develop unclassifiable acute leukemia

• 9% develop B-cell leukemia

• 9% develop biphenotypic leukemia

• loss of Flt3 heterozygosity is seen in leukemias

hematopoietic system

enlarged spleen ( J:189096 )

anemia ( J:189096 )

increased erythroblast number ( J:189096 )

• presence of more than or equal to 20% blasts in blood and blasts in nonhematopoietic organs, including liver and adrenal glands

thrombocytopenia ( J:189096 )

increased leukocyte cell number ( J:189096 )

• mutants develop leukocytosis

immune system

enlarged spleen ( J:189096 )

increased leukocyte cell number ( J:189096 )

• mutants develop leukocytosis

growth/size/body

enlarged spleen ( J:189096 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acute myeloid leukemia		DOID:9119	OMIM:601626	J:189096

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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