mortality/aging
• some tamoxifen-treated mice die between 6 and 20 months of age
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neoplasm
• tamoxifen treated mice have hypersegmented neutrophils, immature cells with myelomonocytic features, nucleated red blood cells, biolobed granulocytes, pseudo-Pelger-Huet cells, and megaplatelets, indicating the presence of myelodysplasia
• 7 of 11 mice exhibit myeloproliferative/myelodysplastic neoplasm within 10 months of tamoxifen treatment similar to human chronic myelomonocytic leukemia
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hematopoietic system
• mice develop splenomegaly 10 months after tamoxifen injection
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• in tamoxifen treated mice
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• increase in number of granulocyte-macrophage progenitor (GMP) cells in the bone marrow of tamoxifen treated mice
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• the number of burst forming unit-erythroid colonies decreases from 14 to 40 weeks of age in tamoxifen treated mice
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• decrease in number of red blood cells in tamoxifen treated mice
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• in tamoxifen treated mice
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• expansion or infiltration of monocytes and granulocytes in the spleen, bone marrow, and liver of tamoxifen treated mice
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• tamoxifen treated mice exhibit expansion of CD11b+Gr1+ neutrophils in spleen
• however, B-cell and T-cell numbers are normal in tamoxifen treated mice
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• decrease in number of platelets in tamoxifen treated mice
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• expansion or infiltration of monocytes and granulocytes in the spleen, bone marrow, and liver of tamoxifen treated mice
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• tamoxifen treated mice exhibit expansion of CD11b+ myeloid cells in spleen
• increase in number of myeloid cells in peripheral blood of tamoxifen treated mice
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• an increase in the number and proportion of hematopoietic stem cells (HSCs), including long-term HSCs and short-term HSCs in the bone marrow of tamoxifen treated mice
• however, the number of bone marrow cells is normal
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• decrease in number of megakaryocyte-erythroid progenitor (MEP) cells in the bone marrow of tamoxifen treated mice
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• increase in serial replating capacity of the bone marrow, LSK (Lin-cKit+Sca1+) and GMP cells from tamoxifen treated mice, indicating an increase in the self-renewal potential of HSCs and progenitor cells
• in vitro assays suggest a differentiation bias of bone marrow and LSK cells toward the myeloid lineage, with an increase in the number of granulocyte-macrophage and granulocyte colonies and decrease in the number of burst forming unit-erythroid colonies
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immune system
• mice develop splenomegaly 10 months after tamoxifen injection
|
• expansion or infiltration of monocytes and granulocytes in the spleen, bone marrow, and liver of tamoxifen treated mice
|
• tamoxifen treated mice exhibit expansion of CD11b+Gr1+ neutrophils in spleen
• however, B-cell and T-cell numbers are normal in tamoxifen treated mice
|
• expansion or infiltration of monocytes and granulocytes in the spleen, bone marrow, and liver of tamoxifen treated mice
|
growth/size/body
• mice develop splenomegaly 10 months after tamoxifen injection
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
chronic myelomonocytic leukemia | DOID:0080188 | J:263565 |