Phenotypes associated with this allele

• Allele Symbol: Kdm6a^tm1Cdcn
• Allele Name: targeted mutation 1, Charlie Degui Chen
• Allele ID: MGI:6192374
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Kdm6a^tm1Cdcn/Y Tg(CAG-cre/Esr1*)5Amc/0 Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S2/SvPas * C57BL/6J * CBA * FVB/N	MGI:6192377
cn2	Kdm6a^tm1Cdcn/Y Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6J * CBA	MGI:6192375
cn3	Kdm6a^tm1Cdcn/Kdm6a^tm1Cdcn Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6J * CBA	MGI:6192376

Genotype
MGI:6192377

cn1

• Allelic Composition: Kdm6a^tm1Cdcn/Y; Tg(CAG-cre/Esr1*)5Amc/0; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * C57BL/6J * CBA * FVB/N

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

mortality/aging

premature death ( J:263565 )

• tamoxifen-treated mice have a median survival of 3.8 months

neoplasm

increased chronic myelocytic leukemia incidence ( J:263565 )

• tamoxifen treated mice develop chronic myelomonocytic leukemia-like disease with a shorter latency than single Kdm6a mutants

hematopoietic system

enlarged spleen ( J:263565 )

• splenomegaly develops 3 months after tamoxifen injection

anemia ( 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 erythrocyte cell number ( J:263565 )

• decrease in number of red blood cells in tamoxifen treated mice which is greater than in either single mutant

increased neutrophil cell number ( J:263565 )

• expansion of neutrophils in the spleen, bone marrow, liver and peripheral blood of tamoxifen treated mice

thrombocytopenia ( J:263565 )

• decrease in number of platelets in tamoxifen treated mice which is greater than in either single mutant

increased monocyte cell number ( J:263565 )

• increase in the number of monocytes in tamoxifen treated mice, which is much greater than in either single mutant

increased myeloid cell number ( J:263565 )

• expansion of myeloid cells in the spleen, bone marrow, liver, and 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) in the bone marrow of tamoxifen treated mice, however the number of bone marrow cells is normal

immune system

enlarged spleen ( J:263565 )

• splenomegaly develops 3 months after tamoxifen injection

increased neutrophil cell number ( J:263565 )

• expansion of neutrophils in the spleen, bone marrow, liver and peripheral blood of tamoxifen treated mice

increased monocyte cell number ( J:263565 )

• increase in the number of monocytes in tamoxifen treated mice, which is much greater than in either single mutant

growth/size/body

enlarged spleen ( J:263565 )

• splenomegaly develops 3 months after tamoxifen injection

Genotype
MGI:6192375

cn2

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

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

• 7 of 11 mice exhibit myeloproliferative/myelodysplastic neoplasm within 10 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

Genotype
MGI:6192376

cn3

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

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