Phenotypes associated with this allele

• Allele Symbol: Flt3^tm1Dgg
• Allele Name: targeted mutation 1, D Gilliland
• Allele ID: MGI:3763385
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Flt3^tm1Dgg/Flt3^tm1Dgg	involves: 129S1/Sv * 129X1/SvJ * BALB/c	MGI:3763426
hm2	Flt3^tm1Dgg/Flt3^tm1Dgg	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3763424
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
cx5	Flt3^tm1Dgg/Flt3^+ Kmt2a^tm1Clgr/Kmt2a^+	involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6J	MGI:5445344
cx6	Flt3^tm1Dgg/Flt3^tm1Dgg Kmt2a^tm1Clgr/Kmt2a^+	involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6J	MGI:5445345

Genotype
MGI:3763426

hm1

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

• ♀: 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

Genotype
MGI:3763424

hm2

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

hematopoietic system

enlarged spleen ( J:126003 )

• mice develop a variable and progressive splenomegaly that is more severe than in heterozygous 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 and heterozygous mice

• 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

• the relative percentage of immunophenotypic granulocyte-monocyte progenitors is expanded while the percent of megakaryocyte-erythroid progenitors is decreased

• however, the total number of myeloid progenitor cells is the same as in wild-type mice

• the proportion of LSK cells in S/G2/M phase is increased while the proportion in G0/G1 is increased compared to in wild-type mice

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

abnormal common myeloid progenitor cell morphology ( J:126003 )

• when cultured on methylcellulose, bone marrow cells produce more colonies than wild-type cells with a greater number of monocytes and fewer erythroid burst forming units and granulocyte-erythroid burst forming units compared to wild-type and heterozygous mice

• however, re-plated colonies do not exhibit increased self-renewal properties

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 more severe than in heterozygous 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 more severe than in heterozygous mice

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

Genotype
MGI:3763427

ht3

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

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

Genotype
MGI:3763425

ht4

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

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

Genotype
MGI:5445344

cx5

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

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

Genotype
MGI:5445345

cx6

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

mortality/aging

premature death ( J:189096 )

• median survival is 19 weeks of age

neoplasm

increased leukemia incidence ( J:189096 )

• 89% develop acute myeloid leukemia

• 11% develop B-cell leukemia

• disease is more aggressive than in double heterozygous mutants

hematopoietic system

enlarged spleen ( J:189096 )

increased leukocyte cell number ( J:189096 )

immune system

enlarged spleen ( J:189096 )

increased leukocyte cell number ( J:189096 )

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