Phenotypes Associated with This Genotype

Genotype
MGI:6192376

• Allelic Composition: Kdm6a^tm1Cdcn/Kdm6a^tm1Cdcn; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6J * CBA

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:263565 )

• some tamoxifen-treated mice die between 6 and 20 months of age

neoplasm

increased chronic myelocytic leukemia incidence ( J:263565 )

• 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

• 9 of 12 mice exhibit myeloproliferative/myelodysplastic neoplasm within 6 months of tamoxifen treatment similar to human chronic myelomonocytic leukemia

hematopoietic system

enlarged spleen ( J:263565 )

• mice develop splenomegaly 10 months after tamoxifen injection

extramedullary hematopoiesis ( J:263565 )

• in tamoxifen treated mice

increased granulocyte monocyte progenitor cell number ( J:263565 )

• increase in number of granulocyte-macrophage progenitor (GMP) cells in the bone marrow of tamoxifen treated mice

decreased erythroid progenitor cell number ( J:263565 )

• the number of burst forming unit-erythroid colonies decreases from 14 to 40 weeks of age in tamoxifen treated mice

decreased erythrocyte cell number ( J:263565 )

• decrease in number of red blood cells in tamoxifen treated mice

increased nucleated erythrocyte cell number ( J:263565 )

• in tamoxifen treated mice

increased granulocyte number ( J:263565 )

• expansion or infiltration of monocytes and granulocytes in the spleen, bone marrow, and liver of tamoxifen treated mice

increased neutrophil cell number ( J:263565 )

• tamoxifen treated mice exhibit expansion of CD11b+Gr1+ neutrophils in spleen

• however, B-cell and T-cell numbers are normal in tamoxifen treated mice

thrombocytopenia ( J:263565 )

• decrease in number of platelets in tamoxifen treated mice

increased monocyte cell number ( J:263565 )

• expansion or infiltration of monocytes and granulocytes in the spleen, bone marrow, and liver of tamoxifen treated mice

increased myeloid cell number ( J:263565 )

• tamoxifen treated mice exhibit expansion of CD11b+ myeloid cells in spleen

• increase in number of myeloid cells in peripheral blood of tamoxifen treated mice

increased hematopoietic stem cell number ( J:263565 )

• 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

decreased megakaryocyte-erythroid progenitor cell number ( J:263565 )

• decrease in number of megakaryocyte-erythroid progenitor (MEP) cells in the bone marrow of tamoxifen treated mice

abnormal hematopoietic stem cell physiology ( J:263565 )

• 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

enlarged spleen ( J:263565 )

• mice develop splenomegaly 10 months after tamoxifen injection

increased granulocyte number ( J:263565 )

• expansion or infiltration of monocytes and granulocytes in the spleen, bone marrow, and liver of tamoxifen treated mice

increased neutrophil cell number ( J:263565 )

• tamoxifen treated mice exhibit expansion of CD11b+Gr1+ neutrophils in spleen

• however, B-cell and T-cell numbers are normal in tamoxifen treated mice

increased monocyte cell number ( J:263565 )

• expansion or infiltration of monocytes and granulocytes in the spleen, bone marrow, and liver of tamoxifen treated mice

growth/size/body

enlarged spleen ( J:263565 )

• 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