Analysis Tools|
Allele Symbol Allele Name Allele ID |
Jak2+ wild type MGI:2431276 |
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| Summary |
13 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• bone marrow exhibits normal CFU-megakaryocyte assays
• mice exhibit normal response to 5-fluorouracil and phenylhydrazine challenge
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• in male, but not female, mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• hematocrit does not differ significantly from controls
• synthesis of new red blood cells following phenylhydrazine hydrolysis is not different from controls
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• in isolated vascular aortic smooth muscle cells, levels of Jak2 autophophorylation are reduced compared to wild-type cells suggesting an inability to activate Jak2
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• bone marrow exhibits normal CFU-megakaryocyte assays
• mice exhibit normal response to 5-fluorouracil and phenylhydrazine challenge
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• in the bone marrow
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• in female, but not male, mice at 8 weeks
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• thrombocythemia in male and female mice at 8 weeks
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• median survival is 146 days
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• all develop a myeloproliferative neoplasm
• these myeloproliferative neoplasms can be transplanted by transfer of either unfractionated bone marrow cells or LSK cells but not by transfer of MEP or granulocyte/macrophage progenitor cells
• however, acute leukemia is not detected
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| N |
• despite the increase in megakaryocyte numbers no increases in platelet counts are detected
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• expansion of the megakaryocytic/erythroid progenitor (MEP) population
• disproportional increase in the number of erythroid progenitors relative to other myeloid progenitor
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• increase in the number of erythroid precursors in the bone marrow and spleen
• marked erythroid hyperplasia in the splenic red pulp
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• prominent splenic extramedullary hematopoiesis
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• megakaryocytes with atypical nuclear features are present in the bone marrow
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• mild hyperplasia in the splenic red pulp
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• overall effacement of the normal architecture
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• marked erythroid and mild megakaryocytic hyperplasia in the splenic red pulp
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• MEPs show EPO hypersensitivity
• gene set enrichment analysis indicates that hematopoietic differentiation in the LSK compartment is altered
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• megakaryocytes with prominent emperipolesis are present in the bone marrow
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• overall effacement of the normal architecture
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• marked erythroid and mild megakaryocytic hyperplasia in the splenic red pulp
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| polycythemia vera | DOID:8997 |
OMIM:263300 |
J:160883 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• all mice die around 30 weeks of age
• mice treated with phenylhydrazine to reduce red blood cells without affecting neutrophils show reversion of lethality
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• mice exhibit extramedullary hematopoiesis
• however, mice do not develop myelofibrosis
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• bone marrow stem cell populations show an expansion of the erythroid progenitor population within myeloid progenitor cell
• however, long-term and short-term hematopoietic stem cells and multipotent progenitor compositions are not affected
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• bone marrow stem cell populations show an expansion of the megakaryocytic progenitor population within myeloid progenitor cells
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• red blood cell mass is roughly tripled by increasing the absolute whole-body red blood cell number
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• erythrocytosis
• bone marrow lineage-negative hematopoietic stem and progenitor cells grown in culture show increased proliferation of erythroid cells
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• leukocytosis, including neutrophilia
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• bone marrow lineage-negative hematopoietic stem and progenitor cells grown in culture show increased proliferation of granulocytic cells
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• moribund mice exhibit widespread large vascular occlusions, prominently in the lungs and kidney
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• moribund mice often show symptoms of thrombosis, including low extremity paralysis and coolness, tachycardia, and tachypnea
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• increase in several proinflammatory cytokines, including CCL3 and CSF1
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• leukocytosis, including neutrophilia
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• bone marrow lineage-negative hematopoietic stem and progenitor cells grown in culture show increased proliferation of granulocytic cells
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• increase in several proinflammatory cytokines, including CCL3 and CSF1
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• low extremity paralysis in moribund mice
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• moribund mice exhibit widespread large vascular occlusions, prominently in the lungs and kidney
• mice treated with repeated injections of Ly-6G antibody to reduce the peripheral neutrophil count do not show alternations in vascular occlusions
• mice treated with phenylhydrazine to reduce red blood cells without affecting neutrophils show a reduction in vascular occlusion formation
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• tachycardia in moribund mice
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| myeloproliferative neoplasm | DOID:2226 | J:257910 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• more than 80% of mice survive beyond 40 weeks
• mice treated with phenylhydrazine to further reduce red blood counts show an even greater improvement in survival
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| N |
• mice exhibit amelioration of the neutrophilia and thrombocytosis, partial reversion of reticulocytosis, mild reduction in red blood cell counts, fewer megakaryocytes and megakaryocyte clusters, reduced spleen size, and reversion of about 25% of the red blood cell expansion seen in single Jak2tm1.1Ble conditional mutants
• bone marrow lineage-negative hematopoietic stem and progenitor cells grown in culture show a reduction in the increased proliferation of erythroid and granulocytic cells seen in single Jak2tm1.1Ble conditional mutants
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• granulocytic differentiation to Gr1/Mac1 double-positive cells is mildly decreased in cultured cells
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• early-stage megakaryocytic differentiation to CD41+ cells is mildly decreased in cultured cells
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| N |
• mice show decreased vascular occlusions than in single Jak2tm1.1Ble conditional mutants, with a decrease in the number of large clots with compact red blood cells and improved blood flow
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| N |
• several proinflammatory cytokines, including CCL3 and CSF1, that are increased in single Jak2tm1.1Ble conditional mutants are reduced
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• granulocytic differentiation to Gr1/Mac1 double-positive cells is mildly decreased in cultured cells
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• erythroid differentiation to Ter119/CD71 double-positive cells is mildly decreased in cultured cells
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• granulocytic differentiation to Gr1/Mac1 double-positive cells is mildly decreased in cultured cells
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• early-stage megakaryocytic differentiation to CD41+ cells is mildly decreased in cultured cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mild at 6 weeks due to an increase in erythroblasts and myeloid cells
• severe at 12 weeks due to an increase in erythroblasts and myeloid cells
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• 3-fold at 6 weeks
• 8-fold at 12 weeks
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• increased CFU-GM in the bone marrow, but not spleen
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• in the spleen
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• in the liver
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• increased BFU-E in the spleen and bone marrow
• however, CFU-E numbers are normal in the bone marrow and spleen
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• mature erythroblasts
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• slightly at 2 weeks
• however, aged mice exhibit a drop in erythrocyte cell number to normal levels
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• at 2 to 3 months and plateau for 5 months
• however, aged mice exhibit a drop in hematocrit to normal levels
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• at 2 months and plateau for 4 months
• however, aged mice exhibit a drop in hemoglobin to normal levels
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• severe
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• severe, plateau for 6 months before decreasing in aged mice
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• early and more so in aged mice
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• at 3 months, mice exhibit increased LSK (2.3 times) and SLAM (2 time) cells in the bone marrow compared with control mice
• at 3 months, mice exhibit increased Lin- (1.5-fold), LSK (1.7-fold) and SLAM (3.7-fold) cells in the spleen compared with control mice
• 1, 3 and 6 month old mice exhibit a 3-, 4- and 5-fold increase, respectively, in total Lin- cells (bone marrow and spleen) compared with control mice
• at 3 months, mice exhibit a 3-fold and 7-fold increase in LSK and SLAM cells, respectively, compared with wild-type mice
• at 6 months, mice exhibit a 4-fold and 6-fold increase in LSK and SLAM cells, respectively, compared with wild-type mice
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• in aged mice
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• in transplantation experiments, bone marrow cells promotes hematopoietic cell proliferation compared to control cells
• however, IFNalpha treatment suppresses increased cell proliferation
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• in aged mice
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• mild at 6 weeks due to an increase in erythroblasts and myeloid cells
• severe at 12 weeks due to an increase in erythroblasts and myeloid cells
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• 3-fold at 6 weeks
• 8-fold at 12 weeks
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• increased CFU-GM in the bone marrow, but not spleen
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• in the spleen
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• early and more so in aged mice
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• in aged mice
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• mild at 6 weeks due to an increase in erythroblasts and myeloid cells
• severe at 12 weeks due to an increase in erythroblasts and myeloid cells
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• 3-fold at 6 weeks
• 8-fold at 12 weeks
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• untreated mice show significantly increased mean spleen weight
• daily treatment with IGF1R kinase inhibitor NVP-AEW541 for 2 months restores spleen weight to wild-type levels
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• untreated mice show significantly increased mean spleen weight
• daily treatment with IGF1R kinase inhibitor NVP-AEW541 for 2 months restores spleen weight to wild-type levels
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• untreated mice show increased platelet number in peripheral blood
• daily treatment with IGF1R kinase inhibitor NVP-AEW541 for 1 or 2 months leads to a significant reduction in peripheral platelet number
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• untreated mice show increased leukocyte number in peripheral blood
• daily treatment with IGF1R kinase inhibitor NVP-AEW541 for 1 or 2 months leads to a significant reduction in peripheral leukocyte number
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• untreated mice show significantly increased % and absolute number of LSK+ cells in the bone marrow
• daily treatment with IGF1R kinase inhibitor NVP-AEW541 for 2 months restores % and absolute number of LSK+ cells in the bone marrow to wild-type levels
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• mice develop myeloproliferative neoplasm (MPN)-associated hematologic phenotypes
• daily treatment with IGF1R kinase inhibitor NVP-AEW541 ameliorates MPN-related phenotypes
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• mice exhibit a 50% reduction in ZFAND2B protein levels and a 2.2-fold increase in IGF1R (insulin-like growth factor I receptor) protein levels relative to wild-type controls
• Zfand2b mRNA levels are reduced in the bone marrow
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• untreated mice show significantly increased mean spleen weight
• daily treatment with IGF1R kinase inhibitor NVP-AEW541 for 2 months restores spleen weight to wild-type levels
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• untreated mice show increased leukocyte number in peripheral blood
• daily treatment with IGF1R kinase inhibitor NVP-AEW541 for 1 or 2 months leads to a significant reduction in peripheral leukocyte number
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increased red blood cell counts
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• high hematocrit
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• mild thrombocytosis
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• elevated reticulocyte counts
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| polycythemia vera | DOID:8997 |
OMIM:263300 |
J:220728 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• decreased numbers of mature erythrocytes
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• decreased numbers of CD4+ T cells
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• decreased numbers of CD8+ T cells
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• elevated reticulocyte counts
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• transferrin/transferrin receptor endocytic rate is decreased as compared to wild-type
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• decreased numbers of CD4+ T cells
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• decreased numbers of CD8+ T cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in 10% of mice following pIpC administration
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• in 10% of mice following pIpC administration
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• at 6 and 26 weeks following pIpC administration, the number of pro-erythrocytes and terminally differentiated erythroblasts is increased compared to in wild-type mice
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• following pIpC administration,10% of mice exhibit increase in Ter119+ erythroid cells in bone marrow (BM), CD71+Ter119+ erythroid cells in the spleen, and Mac1+Gr1+ cells in BM and spleen compared with wild-type mice
• following pIpC administration, one mouse exhibited granulocytic hyperplasia, patchy accumulation of immature cells, reduction of erythroid and megakaryocytic cells, development of collagen fibrosis, decreased Ter119+ erythroid cells in BM, increased CD71+Ter119+ erythroid cells in the spleen, and increased Mac1+Gr1+ cells in BM and spleen compared with wild-type mice
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• 26 weeks following pIpC administration, the number of Gr+Mac1+ cells is modestly increased compared to in wild-type mice
• 10 weeks after pIpC treatment, bone marrow cells exposed to thrombopoietin (TPO) exhibit increased number of ploidy CD41+ cells compared with similarly treated wild-type cells
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• 6 weeks, but not 26 weeks, after pIpC treatment, mice exhibit increased bone marrow-derived colony-forming units-granulocyte, colony-forming units-macrophage, and colony forming units granulocyte-macrophage (CFU-GM) compared with wild-type mice
• however, no TPO-independent megakaryocyte colonies are observed
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• at 6 and 26 weeks following pIpC administration, mice exhibit megakaryocytic hyperplasia with large and hyperlobated forms unlike in wild-type mice
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• modestly at 6 weeks after pIpC treatment in the presence or absence of erythropoietin (EPO)
• significant at 26 weeks after pIpC and EPO treatment with an increase in EPO-independent BFU-E at 26 weeks
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• in 10% of mice following pIpC administration
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• in 10% of mice following pIpC administration
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• following pIpC administration
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• following pIpC administration
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• in one mouse following pIpC administration
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• following pIpC administration
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• after pIpC treatment, mice exhibit reduced numbers of LSK cells compared with wild-type mice
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• after pIpC treatment, LSK cells exhibit increased DNA damage, reduced cell cycling, and reduced apoptosis compared with wild-type mice
• in transplantation assays, hematopoietic stem cells from pIpC treated mice exhibits impaired long-term repopulation compared with wild-type cells
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• in 10% of mice following pIpC administration
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• in one mouse following pIpC administration
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• following pIpC administration
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• following pIpC administration,10% of mice exhibit bone marrow fibrosis unlike wild-type mice
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• 26 weeks following pIpC administration, the number of Gr+Mac1+ cells is modestly increased compared to in wild-type mice
• 10 weeks after pIpC treatment, bone marrow cells exposed to thrombopoietin (TPO) exhibit increased number of ploidy CD41+ cells compared with similarly treated wild-type cells
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| essential thrombocythemia | DOID:2224 |
OMIM:187950 OMIM:601977 OMIM:614521 |
J:164539 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• intermediate in pIpC-treated mice
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• intermediate in pIpC-treated mice
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• increased Gr-1/Mac-1+ cells in the spleen of pIpC-treated mice
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• intermediate increased myeloid, megakaryocyte/erythroid and granulocyte/macrophage progenitors in the bone marrow and spleen of pIpC-treated mice
• increased granulocyte-macrophage progenitors in the spleen of pIpC-treated mice
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• increased myeloid progenitors in the spleen of pIpC-treated mice
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• in the splenic red pulp of pIpC-treated mice
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• in the splenic red pulp of pIpC-treated mice
• 10-fold increase in CD71/Ter-119+ cells in the spleen of pIpC-treated mice
• intermediate in the bone marrow and spleen of pIpC-treated mice
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• intermediate in pIpC-treated mice within 4 weeks and sustained for more than 20 weeks
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• intermediate in pIpC-treated mice
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• in pIpC-treated mice within 4 weeks and sustained for more than 20 weeks
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• in pIpC-treated mice within 4 weeks and sustained for more than 20 weeks
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• in pIpC-treated mice
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• intermediate in pIpC-treated mice
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• in the bone marrow and spleen of pIpC-treated mice
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• intermediate in pIpC-treated mice
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• intermediate in pIpC-treated mice
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• intermediate in pIpC-treated mice
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• in the bone marrow and spleen of pIpC-treated mice
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• slight reticulin fibrosis in pIpC-treated mice
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• in pIpC-treated mice with increased number of megakaryocytes and clusters of immature erythroid precursors
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• fibrosis in pIpC-treated mice
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• fibrosis in the splenic red and white pulp of pIpC-treated mice
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• intermediate in pIpC-treated mice
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• intermediate in pIpC-treated mice
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• increased Gr-1/Mac-1+ cells in the spleen of pIpC-treated mice
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• in the bone marrow and spleen of pIpC-treated mice
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• intermediate in pIpC-treated mice
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• intermediate in pIpC-treated mice
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• slight reticulin fibrosis in pIpC-treated mice
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• in pIpC-treated mice with increased number of megakaryocytes and clusters of immature erythroid precursors
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• fibrosis in pIpC-treated mice
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• fibrosis in the splenic red and white pulp of pIpC-treated mice
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• mild fibrosis in older pIpC-treated mice
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• fibrosis in the bone marrow cavity of pIpC-treated mice
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• intermediate in pIpC-treated mice
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• intermediate in pIpC-treated mice
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| polycythemia vera | DOID:8997 |
OMIM:263300 |
J:183821 | |
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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last database update 01/06/2026 MGI 6.24 |
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