Phenotypes Associated with This Genotype

Genotype
MGI:5558876

• Allelic Composition: Tg(JAK2*V617F)FF1Rsko/0; Tg(Tek-cre)1Arnd/0
• Genetic Background: involves: C57BL/6 * CBA * DBA/2

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

growth/size/body

enlarged spleen ( J:206659 )

• mice develop splenomegaly by 16 weeks of age

hematopoietic system

enlarged spleen ( J:206659 )

• mice develop splenomegaly by 16 weeks of age

abnormal common myeloid progenitor cell morphology ( J:206659 )

• increase in total colony formation, particularly in the number of granulocyte/macrophage (CFU-GM) progenitor cells

abnormal erythropoiesis ( J:206659 )

• decrease in bone marrow erythropoiesis and an increase in splenic erythropoiesis

increased megakaryocyte cell number ( J:206659 )

• CD41/CD61-positive megakaryocytes are increased in the bone marrow and spleen

• greatly increased magakaryopoiesis at 16 weeks of age

abnormal megakaryocyte progenitor cell morphology ( J:206659 )

• increase in total colony formation, particularly in the number of megakaryocyte (CFU-MK) progenitor cells

increased red blood cell distribution width ( J:206659 )

• mice show increased red-cell distribution width without differences in mean cell volume at 22 weeks of age, indicating premyelofibrosis

increased neutrophil cell number ( J:206659 )

• neutrophilia is seen at 8 weeks of age which gets worse by 16 weeks of age

• however no differences in red blood cell or total lymphocyte count is seen

thrombocytosis ( J:206659 )

• thrombocytosis is seen at 8 weeks of age which gets worse by 16 weeks of age

decreased T cell number ( J:206659 )

• reduction in the number of CD3-positive T cells in the bone marrow and spleen

decreased platelet aggregation ( J:206659 )

• blood fails to agglutinate in the presence of ristocetin compared to wild-type

homeostasis/metabolism

abnormal blood homeostasis ( J:206659 )

• plasma levels of von Willebrand Factor (VWF) are normal, however distribution of VWF multimers is different, with mice showing a reduction in ultralarge multimers and a compensatory increase in the levels of smaller VWF multimers

abnormal blood coagulation ( J:206659 )

• blood aggregates quicker and to a greater extent in response to a combination of epinephrine and ADP or collagen than whole blood from wild-type mice, however this is due to increased platelet numbers and not due to increased aggregation and platelets appear to have normal function

decreased platelet aggregation ( J:206659 )

• blood fails to agglutinate in the presence of ristocetin compared to wild-type

decreased susceptibility to induced thrombosis ( J:206659 )

• mice fail to occlude in response to FeCl3 injury over a 30 minute period indicating severely attenuated thrombosis following injury; while platelets adhere to injury site, the platelet plug appears to fail to propagate into an occlusive thrombus

increased bleeding time ( J:206659 )

• increase in bleeding time following injury to the tail compared to wild-type mice

immune system

enlarged spleen ( J:206659 )

• mice develop splenomegaly by 16 weeks of age

increased neutrophil cell number ( J:206659 )

• neutrophilia is seen at 8 weeks of age which gets worse by 16 weeks of age

• however no differences in red blood cell or total lymphocyte count is seen

decreased T cell number ( J:206659 )

• reduction in the number of CD3-positive T cells in the bone marrow and spleen

skeleton

abnormal bone marrow morphology ( J:206659 )

• predominant cell type in the bone marrow is GR1/Mac-1-positive myeloid cells

osteopetrosis ( J:206659 )

• mice develop extensive bone marrow osteopetrosis by 32 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
blood coagulation disease		DOID:1247		J:206659