normal phenotype
• unlike mice heterozygous for Runx1tm1(RUNX1/EVI1)Kmit heterozygotes are viable with no gross abnormalities and normal hematopoietic parameters
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Allele Symbol Allele Name Allele ID |
Runx1+ wild type MGI:1857581 |
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Summary |
20 genotypes
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• unlike mice heterozygous for Runx1tm1(RUNX1/EVI1)Kmit heterozygotes are viable with no gross abnormalities and normal hematopoietic parameters
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• survival of mutants shows slight but significant increase compared to transgenic mice on a wild-type Runx1 background
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• survival of mutants shows slight but significant increase compared to transgenic mice on a wild-type Runx1 background
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• survival of mutants shows slight but significant increase compared to transgenic mice on a wild-type Runx1 background
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• survival of mutants shows slight but significant increase compared to transgenic mice on a wild-type Runx1 background
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice infected with Moloney murine leukemia virus within 24 hours of birth do not show any increase in tumor incidence or latency compared to infected littermate controls
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• at E11.5, animals have a >3-fold decrease in CFU-C in AGM (aorta/gonad/mesonephros) regions than wild-type embryos in the AGM region
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• at E11.5, animals have a >3-fold decrease in CFU-C in AGM (aorta/gonad/mesonephros) regions than wild-type embryos in the AGM region
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• a significant decrease in percentage of CD4+ splenic T cells and in the CD4+:CD8+ ratio is observed compared to wild-type adults, but percentage of CD8+ T cells is not changed
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• a significant decrease in percentage of CD4+ splenic T cells and in the CD4+:CD8+ ratio is observed compared to wild-type adults, but percentage of CD8+ T cells is not changed
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• heterozygotes appear normal, with no observable defects in hematopoietic system development
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• death at approximately E13.5
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• evident at E12.5
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• evident at E12.5
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• failure of embryonic hematopoiesis
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• evident at E12.5
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• evident at E12.5
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• evident at E12.5
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• failure of embryonic hematopoiesis
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• viable and overtly normal, with normal hematocrits, white blood cell differentials, nucleated blood cell count, and distribution of peripheral blood lymphocyte subsets
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• death between E12.5 and E13.5
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• evident at E13.5 in the CNS, the VII/VIII cranial nerve complex and intersegmental regions along the presumptive spinal column
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• embryonic liver
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• fetal liver CFU-C numbers are significantly higher than in Runx1tm1Spe/+ fetuses
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• fetal liver CFU-C numbers are significantly higher than in Runx1tm1Spe/+ fetuses
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• a significant decrease in percentage of CD4+ splenic T cells, and in the CD4+:CD8+ ratio is observed compared to wild-type adults, but percentage of CD8+ T cells is not changed
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• a significant decrease in percentage of CD4+ splenic T cells, and in the CD4+:CD8+ ratio is observed compared to wild-type adults, but percentage of CD8+ T cells is not changed
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• aorta/gonad/mesonephros (AGM) regions have significantly more CFU-C than those in Runx1tm1Spe/+ fetuses
• fetal liver CFU-C numbers are significantly higher than in Runx1tm1Spe/+ fetuses
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• aorta/gonad/mesonephros (AGM) regions have significantly more CFU-C than those in Runx1tm1Spe/+ fetuses
• fetal liver CFU-C numbers are significantly higher than in Runx1tm1Spe/+ fetuses
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• a significant decrease in percentage of CD4+ splenic T cells, and in the CD4+:CD8+ ratio is observed compared to wild-type adults, but percentage of CD8+ T cells is not changed
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• a significant decrease in percentage of CD4+ splenic T cells, and in the CD4+:CD8+ ratio is observed compared to wild-type adults, but percentage of CD8+ T cells is not changed
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• at E11.5, numbers of CFU-C is reduced slightly more than in Runx1tm1Spe/+ fetuses but is significantly less than in Runx1tm6Spe/+ fetuses
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• at E11.5, numbers of CFU-C is reduced slightly more than in Runx1tm1Spe/+ fetuses but is significantly less than in Runx1tm6Spe/+ fetuses
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• animals have a smaller percentage of CD4+ cells and a lower CD4+:CD8+ ratio than Runx1tm1Spe/+ adults
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• animals have a smaller percentage of CD4+ cells and a lower CD4+:CD8+ ratio than Runx1tm1Spe/+ adults
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• aorta/gonad/mesonephros (AGM) regions have significantly more CFU-C than those in Runx1tm1Spe/+ fetuses
|
• aorta/gonad/mesonephros (AGM) regions have significantly more CFU-C than those in Runx1tm1Spe/+ fetuses
|
• a significant decrease in percentage of CD4+ splenic T cells, and in the CD4+:CD8+ ratio is observed compared to wild-type adults, but percentage of CD8+ T cells is not changed
|
• a significant decrease in percentage of CD4+ splenic T cells, and in the CD4+:CD8+ ratio is observed compared to wild-type adults, but percentage of CD8+ T cells is not changed
|
|
|
♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• a significant decrease in percentage of CD4+ splenic T cells, and in the CD4+:CD8+ ratio is observed compared to wild-type adults, but percentage of CD8+ T cells is not changed
|
• a significant decrease in percentage of CD4+ splenic T cells, and in the CD4+:CD8+ ratio is observed compared to wild-type adults, but percentage of CD8+ T cells is not changed
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• at E10.5, 10% of embryos are found dead while at E14.5, all mutant heterozygotes are dead; data indicates embryos die ~E13.5 from CNS hemorrhage
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• liver at E12.5 shows near complete absence of erythroid, myeloid, or megakaryocytic progenitors
• cultured E12.5 fetal liver cells give rise only to macrophage colonies whereas wild-type cells produce multilineage colonies; E13.5 cells give rise to numerous mixed-like colonies
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• liver at E12.5 shows near complete absence of erythroid, myeloid, or megakaryocytic progenitors
• cultured E12.5 fetal liver cells give rise only to macrophage colonies whereas wild-type cells produce multilineage colonies; E13.5 cells give rise to numerous mixed-like colonies
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• postenucleated erythrocytes are absent from peripheral blood of mutant embryos, but are present in wild-type littermates
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• postenucleated erythrocytes are absent from peripheral blood of mutant embryos, but are present in wild-type littermates
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• hemorrhage occurs as early as E12.5 in the cerebral ventricle, as well as the dorsal root ganglia
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• hemorrhage occurs as early as E12.5 in the cerebral ventricle, as well as the dorsal root ganglia
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• significantly lower than in controls
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• significantly lower than in controls
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• following treatment with pIpC, the number of progenitors, enriched hematopoietic stem cells, and pure hematopoietic stem cells are increased compared to similarly treated wild-type mice
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• fewer than expected mice are present at weaning
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• bone marrow cells from pIpC-induced mice form fewer granulocyte-macrophage positive colonies than when wild-type cells are used
• bone marrow cells transplanted into wild-type mice and induced with pIpC fail to reconstitute multiple hematopoietic lineages
• however, treatment with imatinib restores the ability of pIpC-treated bone marrow cells to induce long-term multiple lineages reconstitution in transplantation experiments
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• bone marrow cells from pIpC-induced mice form fewer granulocyte, erythrocyte, macrophage, and megakaryocyte positive colonies than when wild-type cells are used
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• all pIpC-induced mice develop a chronic myelocytic leukemia (CML)-like myeloproliferative disease
• bone marrow cells activated with pIpC induce develop a CML-like myeloproliferative disease when transplanted into wild-type mice
• however, secondary transplantation of neoplastic cells or fractionated splenocytes are highly inefficient at inducing myeloproliferative disease
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• in pIpC-induced mice
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• 2 weeks after pIpC induction, bone marrow and spleens exhibit a decreased in the frequency of lymphoid and erythroid lineages but an increase in myeloid lineages compared to control mice
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• in pIpC-induced mice despite treatment with imatinib
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• after pIpC induction, mice exhibit severe myeloid leukocytosis with a 25-fold increase in white blood cells compared with similarly treated wild-type mice
• however, treatment with imatinib reduces white blood cell counts to wild-type levels
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• the number of Mac1+Gr1+ myeloid cells in the spleen and bone marrow of pIpC-induced mice is increased compared to in wild-type mice
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• severe following pIpC induction
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• the frequency of hematopoietic stem cells in the bone marrow of pIpC-induced mice is decreased compared to in wild-type mice
• the number of hematopoietic stem cells in the bone marrow of pIpC-induced mice is less than in wild-type mice
• bone marrow cells transplanted into wild-type mice and activated with pIpC inhibit normal bone marrow hematopoietic stem cells and result in a decrease in donor and recipient-type hematopoietic stem cells compared to when wild-type bone marrow cells are transplanted
• however, treatment of pIpC-induced mice with imatinib returns the frequency of hematopoietic stem cell to near normal even in transplantation experiments
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• the absolute number of hematopoietic stem cells in the spleen is increased in pIpC-induced mice compared to in wild-type mice
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• pIpC-induced mice exhibit splenic architecture effacement unlike similarly treated wild-type mice
• however, treatment with imatinib returns spleen architecture to normal
• 2 weeks after pIpC induction, bone marrow and spleens exhibit a decreased in the frequency of lymphoid and erythroid lineages but an increase in myeloid lineages compared to control mice
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• 10-fold 72 hours after pIpC induction unlike similarly treated wild-type mice
• however, treatment with imatinib reduces liver size to wild-type and clears neoplastic cells
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• following pIpC induction
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• in pIpC-induced mice
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• in pIpC-induced mice
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• pIpC-induced mice loss organized splenic follicle cells unlike similarly treated wild-type mice
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• when bone marrow cells are transplanted into recipient mice and induced with pIpC recipient mice exhibit enlarge spleen, effacement of spleen architecture, and increased white blood cell counts compared to when mice are transplanted with control bone marrow cells lacking the cre transgene
• however, treatment with imatinib decreased white blood cell counts in recipients following pIpC-induction of transplanted bone marrow cells
• bone marrow cells transplanted into wild-type mice and activated with pIpC inhibit normal bone marrow hematopoietic stem cells and result in a decrease in donor and recipient-type hematopoietic stem cells compared to when wild-type bone marrow cells are transplanted
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• neoplastic cells in the livers and spleens of pIpC-induced mice are positive for proliferative markers
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• 25% of un-induced mice develop a chronic myelocytic leukemia (CML)-like disease unlike control mice
• pIpC-induced mice exhibit a CML-like myeloproliferative disease unlike similarly treated wild-type mice
• bone marrow cells activated with pIpC induce develop a CML-like myeloproliferative disease when transplanted into wild-type mice
• however, secondary transplantation of neoplastic cells or fractionated splenocytes are highly inefficient at inducing myeloproliferative disease
• treatment with imatinib increases the frequency of leukemia initiating cells in transplantation experiments with pIpC-activated whole bone marrow cells and hematopoietic stem cells and results in greater incidence of CML-like disease
• leukemia cells infiltrate the lungs in pIpC-induced mice
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• pIpC-induced mice exhibit mature myeloid cells surrounding portal cavities and infiltrating the parenchyme unlike in similarly treated wild-type mice
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• 2-fold 72 hours after pIpC induction unlike similarly treated wild-type mice
• however, treatment with imatinib reduces liver size to wild-type and clears neoplastic cells
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• following pIpC induction
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• pIpC-induced mice exhibit mature myeloid cells infiltrating the parenchyme unlike in similarly treated wild-type mice
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• pIpC-induced mice exhibit mature myeloid cells infiltrating the lungs unlike in similarly treated wild-type mice
• leukemia cells infiltrate the lungs in pIpC-induced mice
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• all pIpC-induced mice develop a chronic myelocytic leukemia (CML)-like myeloproliferative disease
• bone marrow cells activated with pIpC induce develop a CML-like myeloproliferative disease when transplanted into wild-type mice
• however, secondary transplantation of neoplastic cells or fractionated splenocytes are highly inefficient at inducing myeloproliferative disease
|
• after pIpC induction, mice exhibit severe myeloid leukocytosis with a 25-fold increase in white blood cells compared with similarly treated wild-type mice
• however, treatment with imatinib reduces white blood cell counts to wild-type levels
|
• the number of Mac1+Gr1+ myeloid cells in the spleen and bone marrow of pIpC-induced mice is increased compared to in wild-type mice
|
• severe following pIpC induction
|
• pIpC-induced mice exhibit splenic architecture effacement unlike similarly treated wild-type mice
• however, treatment with imatinib returns spleen architecture to normal
• 2 weeks after pIpC induction, bone marrow and spleens exhibit a decreased in the frequency of lymphoid and erythroid lineages but an increase in myeloid lineages compared to control mice
|
• 10-fold 72 hours after pIpC induction unlike similarly treated wild-type mice
• however, treatment with imatinib reduces liver size to wild-type and clears neoplastic cells
|
• following pIpC induction
|
• in pIpC-induced mice
|
• in pIpC-induced mice
|
• pIpC-induced mice loss organized splenic follicle cells unlike similarly treated wild-type mice
|
• 2-fold 72 hours after pIpC induction unlike similarly treated wild-type mice
• however, treatment with imatinib reduces liver size to wild-type and clears neoplastic cells
|
• following pIpC induction
|
• 10-fold 72 hours after pIpC induction unlike similarly treated wild-type mice
• however, treatment with imatinib reduces liver size to wild-type and clears neoplastic cells
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• following pIpC induction
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• in pIpC-induced mice
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• 50% of mice die between 6-12 months of age
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• prior to death mice exhibit neutrophilia and/or moncytosis
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• prior to death mice exhibit thrombocytopenia
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• prior to death mice exhibit lymphopenia
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• prior to death mice exhibit neutrophilia and/or moncytosis
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• prior to death mice exhibit neutrophilia and/or moncytosis
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• prior to death mice exhibit lymphopenia
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• prior to death mice exhibit neutrophilia and/or moncytosis
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mice treated with pI:pC and ENU die rapidly between 2 and 10 months coincident with tumor presentation
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• 47% of 5-10 week old mice treated with pI:pC then treated with ENU develop hematopoietic neoplasms 2-10 months after treatment
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• some pI:pC and ENU treated mice develop thymic derived T cell lymphoblastic lymphomas (17%)
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• some pI:pC and ENU treated mice develop granulocytic sarcoma/acute myeloid leukemia (30%)
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• some pI:pC and ENU treated mice develop granulocytic sarcoma/acute myeloid leukemia (30%); these are solid masses of proliferating myeloblasts which form in retroperitoneum, soft tissue, or in bones of sternum, cranium, or extremities adjacent to soft tissue
• tumor cells disseminate widely, with clusters of cells found in spleen, liver, kidney and lymph nodes
• in some mice, increased myeloblasts are observed in bone marrow, as well as markedly increased white blood cell counts with identifiable circulating leukemic blasts
• tumors are transplantable
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• some pI:pC and ENU treated mice develop thymic derived T cell lymphoblastic lymphomas (17%)
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N |
• mimimal abnormalities in hematopoiesis are observed in mutants expressing the Runx1 knock-in allele after pI:pC treatment, although a slight increase in granulocyte-monocyte, mixed and total colonies, as well as in day 12 CFUs in bone marrow, is seen
• no leukemia develops during the first 11months of life of treated mutants
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• 2 mice develop hematopoietic neoplasms by 1 year of age (1 T cell lymphoma, 1 undifferentiated lymphoma)
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• some pI:pC and ENU treated mice develop thymic derived T cell lymphoblastic lymphomas (17%)
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• bone marrow cells isolated from mice treated with pI:pC show enhanced replating efficiency in culture; cells are able to form myeloid colonies long after wild-type cells have stopped growing
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• some pI:pC and ENU treated mice develop thymic derived T cell lymphoblastic lymphomas (17%)
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mice were viable and showed no malignancies within 5 months of birth
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mice exhibit fewer large GFP+ hematopoietic cells or clusters in the dorsal aorta compared with Tg(Runx1-GFP)#Itan mice
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• mice exhibit fewer large GFP+ hematopoietic cells or clusters in the dorsal aorta compared with Tg(Runx1-GFP)#Itan mice
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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 03/18/2025 MGI 6.24 |
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