mortality/aging
• unable to obtain any viable homozygotes, with the stage of prenatal lethality not specified
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Allele Symbol Allele Name Allele ID |
Jak2tm1.1Ble targeted mutation 1.1, Benjamin L Ebert MGI:4818800 |
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Summary |
3 genotypes
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• unable to obtain any viable homozygotes, with the stage of prenatal lethality not specified
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• 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 |
• 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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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 11/19/2024 MGI 6.24 |
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