Mouse Genome Informatics
cn
    Atg7tm1Tchi/Atg7tm1Tchi
Tg(Vav1-cre)A2Kio/0

involves: C57BL/6NCrlj * C57BL/10 * CBA/Ca * CBA/JNCrlj
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
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
• 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
• 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
• overall bone marrow cell count is reduced
• mutant LSK (Lin-Sca-1+c-Kit+) cells accumulate mitochondria, mitochondrial superoxide, and DNA damage and exhibit increased levels of apoptosis and proliferation
• 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
• 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

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
• 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

Mouse Models of Human Disease
OMIM IDRef(s)
Myelodysplastic Syndrome; MDS 614286 J:176843