hematopoietic system
• reduction in most myeloid progenitors
• numbers of myeloid subsets CD11b+Gr1- and CD11b-Gr1+ are reduced in blood and decrease further over time
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• overall bone marrow cell count is reduced
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• common lymphoid progenitors (Lin-Flt3HighIL7RaHighSca-1Lowc-KitLow) are reduced in mutants
• numbers of CCR9+ lymphoid-primed multipotent progenitors are reduced in the bone marrow of mutants
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• mutant LSK (Lin-Sca-1+c-Kit+) cells accumulate mitochondria, mitochondrial superoxide, and DNA damage and exhibit increased levels of apoptosis and proliferation
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• numbers of hematopoietic stem cells are reduced in all mutants, regardless of disease progression
• absolute numbers of LSK (Lin-Sca-1+c-Kit+) cells significantly increased in asymptomatic 7 week old mutants, however as they develop symptoms, the frequency of LSK cells falls to wild-type levels
• the Lin-Sca-1-c-Kit+ (LK) compartment, containing more mature hematopoietic progenitors, is decreased
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• numbers of CD11b+Gr1+ cells are increased in the blood at 5 and 6 weeks of age but then decrease to below wild-type levels at 8 weeks of age
• CD11b+Gr1+ cells in the spleen and bone marrow are increased and show higher proliferation rates
• mutants exhibit presence of atypical myeloid infiltrates in a wide range of organs
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• mutants are cytopenic for all blood leukocyte populations except for CD11b+Gr1+ cells
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• absolute cell counts of B cells are decreased in the peripheral blood of mutants and numbers drop steadily over time
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• immature NK cells (Lin-CD3-CD122+NK1.1+DX5+) are depleted in the bone marrow
• absolute cell counts of NK cells are decreased in the peripheral blood of mutants and numbers drop steadily over time
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• absolute cell counts of T cells are decreased in the peripheral blood of mutants and numbers drop steadily over time
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• adult bone marrow cells from mutants transplanted together with CD45.1+ wild-type bone marrow cells into lethally irradiated wild-type hosts fail to contribute to reconstitution of cells in the hosts while in noncompetitive reconstitution experiments, lethally irradiated mice die within 4 weeks after transplantation with mutant bone marrow cells, indicating loss of hematopoietic stem cell activity
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immune system
• numbers of CD11b+Gr1+ cells are increased in the blood at 5 and 6 weeks of age but then decrease to below wild-type levels at 8 weeks of age
• CD11b+Gr1+ cells in the spleen and bone marrow are increased and show higher proliferation rates
• mutants exhibit presence of atypical myeloid infiltrates in a wide range of organs
|
• mutants are cytopenic for all blood leukocyte populations except for CD11b+Gr1+ cells
|
• absolute cell counts of B cells are decreased in the peripheral blood of mutants and numbers drop steadily over time
|
• immature NK cells (Lin-CD3-CD122+NK1.1+DX5+) are depleted in the bone marrow
• absolute cell counts of NK cells are decreased in the peripheral blood of mutants and numbers drop steadily over time
|
• absolute cell counts of T cells are decreased in the peripheral blood of mutants and numbers drop steadily over time
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
myelodysplastic syndrome | DOID:0050908 |
OMIM:614286 |
J:176843 |