Table 5.
Hematological-related mouse phenotypes found in BMF/HM predisposition genes including strong candidate genes and other candidate genes.
| TF gene symbol |
MGI Mouse Phenotype (Hematological) | |
|---|---|---|
| Phenotype | ||
| Known BMF/HM TFs | Runx1 |
- abnormal hematopoiesis-related cell morphology/development/number, hematopoietic differentiation, and spleen/thymus size/morphology - Thrombocytopenia |
| Cebpa | - enlarged spleen - abnormal definitive hematopoiesis, myelopoiesis, granulocyte, leukocyte common myeloid progenitor and bone marrow cell morphology and myeloid leukocyte - increased erythroid progenitor, hematopoietic, neutrophil, granulocyte, monocyte cell number and decreased hematocrit |
|
| Gata2 |
- abnormal embryonic/definitive hematopoiesis, blood cell/megakaryocyte morphology/development and stress erythropoiesis/hematopoiesis - decreased common myeloid/erythroid progenitor cell number - anemia |
|
| Pax5 |
- abnormal lymphopoiesis, class switch recombination, B/T cell number/differentiation/physiology, immunoglobulin heavy chain V(D)J recombination and macrophage, monocyte and leukocyte cell number - decreased immunoglobulin and IgA, IgD, IgG1, IgG2a, IgG2b, IgG3, IgG, IgM levels |
|
| Mecom/Evi1 |
- abnormal neutrophil differentiation, common myeloid progenitor cell morphology/number, bone marrow cell morphology/development, platelet, HSC and fetal liver HPC morphology and leukocyte, HSC, precursor and B-cell numbers - thrombocytopenia |
|
| Stat3 | - abnormal thymocyte, T cell apoptosis/proliferation, thymocyte, neutrophil, dendritic cell, T- granulocyte, macrophage, monocyte and leukocyte cell number, T cell, macrophage differentiation/physiology and IgE, IgG1 and IgG3 levels | |
| Gata1 |
- abnormal embryonic erythropoiesis, definitive hematopoiesis and megakaryocyte differentiation, spleen, common myeloid progenitor cell, megakaryocyte, proerythroblast, erythrocyte, platelet, mononuclear, spleen, bone marrow cell and erythroid progenitor morphology, erythropoiesis, myelopoiesis, thrombopoiesis and extramedullary hematopoiesis, bone marrow, megakaryocyte, erythroid progenitor, eosinophil, erythrocyte, neutrophil, leukocyte, lymphocyte, osteoclast and splenocyte cell numbers, and hemocrit - anemia, anisocytosis, poikilocytosis, polychromatophilia and thrombocytopenia |
|
|
Etv6
(Tel) |
- abnormal megakaryocyte, B cell differentiation, definitive hematopoiesis, erythropoiesis and lymphopoiesis, spleen, common myeloid progenitor, lymphocyte progenitor cell and myeloblast morphology, erythroid progenitor, erythrocyte, neutrophil cell, B cell, lymphocyte and HSC cell numbers and bone marrow cell physiology - myeloid hyperplasia and thrombocytopenia |
|
| Fli1 |
- abnormal megakaryocyte, B cell differentiation, erythropoiesis, thrombopoiesis and hematopoiesis, thymocyte, B cell, megakaryocyte, erythroid progenitor, erythrocyte, granulocyte, NK and monocyte cell numbers, spleen and megakaryocyte, proerythroblast and leukocyte morphology - decreased B cell proliferation, hematocrit and IgG1 and IgG3 levels - anemia and thrombocytopenia |
|
| Ikzf1 |
- abnormal B cell apoptosis, granulocyte, macrophage and B/T cell differentiation, B/T cell proliferation, thymus and spleen, definitive hematopoiesis, erythropoiesis, lymphopoiesis and myelopoiesis, common myeloid progenitor cell morphology, B/T, bone marrow, erythroid progenitor, basophil, erythrocyte, granulocyte, dendritic, NK cell, macrophage and splenocyte cell numbers, erythroid progenitor cell, eosinophil, erythroblast and NK morphology, and natural killer cell mediated cytotoxicity. - myeloid hyperplasia, extramedullary hematopoiesis and anemia - decreased hematocrit, hemoglobin content and IgG3 and IgG levels |
|
| Ikzf3 |
- abnormal B/T cell proliferation and differentiation, spleen, neutrophil, B- cell, lymphocyte and leukocyte cell numbers and IgE, IgG1, IgG2a, IgG2b, IgG3 and IgM levels - thrombocytopenia |
|
| Ikzf5 |
- Abnormal IgA and IgE levels - Epistaxisl, Joint hemorrhages, Persistent bleeding after trauma, Bruising susceptibility, Petechiae, Anemia of inadequate production, Poikilocytosis, Acanthocytosis, Leukocytosis and Thrombocytopenia - Increased megakaryocyte colony forming unit counts |
|
| Strong candidate BMF/HM TFs | Gata3 | - increased T cell apoptosis and decreased IgE levels - abnormal thymus, thymocyte, T- and eosinophil cell numbers, definitive hematopoiesis, and T cell differentiation/morphology |
|
Spi1
(Pu.1) |
- abnormal granulocyte, neutrophil, macrophage, and B/T cell differentiation, thymus and spleen, blood cell, bone marrow common myeloid progenitor, T-cell, proerythroblast, granulocyte, microglial, monocyte and spleen morphology, definitive hematopoiesis, erythropoiesis, leukopoiesis and myelopoiesis, B/T-, bone marrow, erythrocyte, granulocyte, neutrophil, Lymphocyte, macrophage, HSC cell numbers and HSC physiology. - increased hematopoietic stem cell proliferation, mean corpuscular volume and IgM level, and decreased thymocyte number and hematocrit - absent common myeloid progenitor cells and anemia and extramedullary hematopoiesis |
|
| Erg |
- abnormal embryonic erythropoiesis, spleen morphology and leukocyte, HSC and B cell numbers (decreased) - thrombocytopenia and pancytopenia |
|
| Other candidate BMF/HM TFs | Etv2 |
- abnormal spleen, embryonic erythropoiesis, definitive hematopoiesis, myelopoiesis, bone marrow and myeloblast morphology/development, common myeloid progenitor, bone marrow, erythroid progenitor, leukocyte and HSC cell number and absent erythrocytes - anemia |
| Elf1 | - abnormal B cell differentiation and B cell physiology | |
| Fev | No Hematological phenotype reported | |
| Ets1 |
- abnormal B cell, thymocyte, splenocyte apoptosis, B/T cell proliferation, thymus and spleen, lymphopoiesis, B cell differentiation, B/T-, plasma, NK, leukocyte cell numbers, leukocyte, NK cell physiology and T cell activation - impaired natural killer cell mediated cytotoxicity |
|
| Ets2 | No Hematological phenotype reported | |
| Ikzf2 | - abnormal regulatory T cell physiology | |
| Ikzf4 | - decreased T cell proliferation and increased immunoglobulin level - abnormal spleen and B/T cell number |
|
| Gfi1b |
- abnormal megakaryocyte differentiation and erythropoiesis, blood, bone marrow cell morphology/development, erythroid progenitor, erythrocyte, neutrophil, lymphocyte, HSC, splenocyte cell numbers, megakaryocyte progenitor and embryonic erythrocyte cell morphology and hemoglobin content (decreased) - anemia and thrombocytopenia |
|
|
Tal1
(SCL) |
- abnormal embryonic hematopoiesis and erythropoiesis, thymus and spleen, common myeloid progenitor, bone marrow, leukocyte, and HSC cell numbers and bone marrow, megakaryocyte, erythroid progenitor and proerythroblast cell morphology - anemia, anisocytosis and thrombocytopenia - decreased hematocrit and hemoglobin content, mean corpuscular hemoglobin concentration and mean corpuscular volume |
|
| Lyl1 |
- abnormal B/T cell number/differentiation and hematopoietic stem cell physiology - thrombocytopenia |
|
| Lmo2 |
- abnormal embryonic hematopoiesis, thymus and spleen, common myeloid progenitor and megakaryocyte progenitor cell morphology, erythrocyte, granulocyte and monocyte cell number - decreased hemoglobin content, increased mean corpuscular volume - thrombocytopenia |
|
| Meis1 | - decreased common myeloid progenitor, megakaryocyte, platelet cell number - abnormal bone marrow and megakaryocyte progenitor cell morphology - increased hematopoietic stem cell number |
|
| Tcf12 | - thymus hypoplasia - abnormal thymocyte B/T cell number and morphology - arrested T cell differentiation |
|
| Gfi1 | - abnormal granulocyte, monocyte, NK and T-cell differentiation, T cell proliferation, thymus, thymocyte, T/B-cell neutrophil, granulocyte, monocyte and HSC number, definitive hematopoiesis, lymphopoiesis and myelopoiesis, neutrophil and monocyte morphology and NK cell and T-helper physiology | |
| Fos | - increased macrophage apoptosis - abnormal osteoclast differentiation, thymus and spleen, thymocyte, T/B-cell, granulocyte, splenocyte and osteoclast cell number, lymphopoiesis and macrophage physiology |
|
| Hoxa9 | - abnormal common myeloid progenitor cell morphology, bone marrow and HSC cell number and spleen | |
| Fosb | No Hematological phenotype reported | |
| Foxc2 | No Hematological phenotype reported | |
| Eklf (Klf1) |
- abnormal spleen, erythropoiesis, hematopoiesis and erythroblastosis, erythrocyte morphology and cell number - decreased hematocrit, hemoglobin content, mean corpuscular hemoglobin - anemia, anisocytosis, poikilocytosis and polychromatophilia |
|
| Nfkb1 |
- abnormal spleen, B/T cell proliferation, bone marrow cell morphology/development, erythrocyte, B/T-, NK, myeloid dendritic, osteoclast and leukocyte cell number, lymphocyte, B/T cell and macrophage physiology, IgA, IgE, IgG1, IgG3, IgG, IgM and immunoglobulin levels and CD4-positive, alpha-beta T cell physiology - myeloid hyperplasia and decreased mean corpuscular hemoglobin concentration |