Phenotypes Associated with This Genotype

Genotype
MGI:5444038

• Allelic Composition: Tg(H2-K^b-Jak2*V617F)2Shmd/0
• Genetic Background: involves: C57BL/6 * DBA/2

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

hematopoietic system

abnormal definitive hematopoiesis ( J:130189 )

• increase in number of CD41+ cells and Gr-1/Mac1 double-positive cells in the bone marrow and spleen

• decrease in the number of CD71/TER119 double-positive cells

• decrease in the percentage of B220+ B cells in the bone marrow and spleen

myeloid hyperplasia ( J:130189 )

• increase in numbers of mature myeloid cells in spleen

• femurs exhibit prominent population of maturing myeloid cells

anemia ( J:130189 )

abnormal megakaryocyte morphology ( J:130189 )

• megakaryoctyes of many sizes are clustered and show unusual morphology, including aberrant nuclear-to-cytoplasmic ratio, emperipolesis of neutrophils in megakaryocyte cytoplasm, and bulbous or irregularly folded nuclei

increased megakaryocyte cell number ( J:130189 )

• femurs exhibit prominent population of maturing myeloid cells with a moderate increase in megakaryocyte numbers

decreased erythroid progenitor cell number ( J:130189 )

• decrease in the percentage of erythroid precursor cells in the bone marrow

decreased erythroblast number ( J:130189 )

• decrease in the percentage of erythroblasts in spleen

decreased erythrocyte cell number ( J:130189 )

• number of red blood cells is decreased at 1 month of age with the greatest decrease at 9 months of age

decreased hematocrit ( J:130189 )

• hematocrit is decreased at 1 month of age, with a further decrease at 6 months

decreased hemoglobin content ( J:130189 )

increased number of Howell-Jolly bodies ( J:130189 )

polychromatophilia ( J:130189 )

thrombocytosis ( J:130189 )

• thrombocytosis is seen at 1 months of age, however platelet counts slowly decline with age and return to near-normal levels at 8 months of age

giant platelets ( J:130189 )

• peripheral blood shows giant platelets

increased leukocyte cell number ( J:130189 )

• mutants exhibit severe leukocytosis at 1 month of age; leukocyte numbers increase with age, with leukocytosis peaking at 5 months of age and then slightly decreasing afterwards but still remaining higher than in controls

increased neutrophil cell number ( J:130189 )

• majority of increased leukocytes are mature neutrophils with some immature cells

• increase in the percentage of neutrophil precursor cells in the bone marrow

abnormal spleen morphology ( J:130189 )

• complete effacement of normal splenic architecture, with invasion of non-lymphoid cells

enlarged spleen ( J:130189 )

• splenomegaly is seen at 3-5 months of age

increased spleen weight ( J:130189 )

increased spleen red pulp amount ( J:130189 )

• the red pulp is expanded by an atypical population of maturing myeloid cells and megakaryocytes and few erythroblasts

spleen fibrosis ( J:130189 )

• fibrosis in the spleen, with mild accumulation of fibers at 6 months of age and development of fibrosis by 9 months of age

enhanced megakaryocyte emperipolesis ( J:130189 )

• emperipolesis of neutrophils in megakaryocyte cytoplasm is observed in femurs

immune system

myeloid hyperplasia ( J:130189 )

• increase in numbers of mature myeloid cells in spleen

• femurs exhibit prominent population of maturing myeloid cells

increased leukocyte cell number ( J:130189 )

• mutants exhibit severe leukocytosis at 1 month of age; leukocyte numbers increase with age, with leukocytosis peaking at 5 months of age and then slightly decreasing afterwards but still remaining higher than in controls

increased neutrophil cell number ( J:130189 )

• majority of increased leukocytes are mature neutrophils with some immature cells

• increase in the percentage of neutrophil precursor cells in the bone marrow

abnormal spleen morphology ( J:130189 )

• complete effacement of normal splenic architecture, with invasion of non-lymphoid cells

enlarged spleen ( J:130189 )

• splenomegaly is seen at 3-5 months of age

increased spleen weight ( J:130189 )

increased spleen red pulp amount ( J:130189 )

• the red pulp is expanded by an atypical population of maturing myeloid cells and megakaryocytes and few erythroblasts

spleen fibrosis ( J:130189 )

• fibrosis in the spleen, with mild accumulation of fibers at 6 months of age and development of fibrosis by 9 months of age

skeleton

myelofibrosis ( J:130189 )

• mutants develop fibrosis in the bone marrow with age

increased compact bone thickness ( J:130189 )

• bone cortical thickness is mildly increased, with newly formed bony trabeculae, in 6 month old mice

growth/size/body

enlarged spleen ( J:130189 )

• splenomegaly is seen at 3-5 months of age

increased spleen weight ( J:130189 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
myelofibrosis		DOID:4971	OMIM:254450	J:130189