Phenotypes Associated with This Genotype

Genotype
MGI:3763424

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

• ♀: 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 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