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Phenotypes Associated with This Genotype
Genotype
MGI:6192375
Allelic
Composition
Kdm6atm1Cdcn/Y
Tg(CAG-cre/Esr1*)5Amc/0
Genetic
Background
involves: C57BL/6J * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Kdm6atm1Cdcn mutation (0 available); any Kdm6a mutation (36 available)
Tg(CAG-cre/Esr1*)5Amc mutation (6 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• some tamoxifen-treated mice die between 6 and 20 months of age

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

hematopoietic system
• in tamoxifen treated mice
• increase in number of granulocyte-macrophage progenitor (GMP) cells in the bone marrow of tamoxifen treated mice
• the number of burst forming unit-erythroid colonies decreases from 14 to 40 weeks of age in tamoxifen treated mice
• decrease in number of red blood cells in tamoxifen treated mice
• in tamoxifen treated mice
• expansion or infiltration of monocytes and granulocytes in the spleen, bone marrow, and liver of tamoxifen treated mice
• however, B-cell and T-cell numbers are normal in tamoxifen treated mice
• tamoxifen treated mice exhibit expansion of CD11b+Gr1+ neutrophils in spleen
• decrease in number of platelets in tamoxifen treated mice
• 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+ myeloid cells in spleen
• increase in number of myeloid cells in peripheral blood of tamoxifen treated mice
• 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
• decrease in number of megakaryocyte-erythroid progenitor (MEP) cells in the bone marrow of tamoxifen treated mice
• mice develop splenomegaly 10 months after tamoxifen injection
• 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

immune system
• 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
• mice develop splenomegaly 10 months after tamoxifen injection

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
chronic myelomonocytic leukemia DOID:0080188 J:263565


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
10/09/2018
MGI 6.12
The Jackson Laboratory