reproductive system
• decrease in numbers of spermatocytes and spermatids
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• 2 month old females show degenerated follicles
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small ovary
(
J:224688
)
• in 2 month old mice
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small testis
(
J:224688
)
• in 2 month old mice
|
cellular
• decrease in numbers of spermatocytes and spermatids
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• bone marrow hematopoietic stem cells and progenitor cells are more sensitive to genotoxic stress resulting from DNA crosslinks induced with mitomycin C
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• embryonic fibroblasts (MEFs) from E11.5 embryos show an accumulation of G2M phase both at baseline and upon mitomycin C treatment, indicating a G2M arrest at both steady and stressed stages
• MEFs undergo less severe G2M arrest than homozygous Fancatm1.1Wong or
Fancctm1Mab MEFs and exhibit less apoptosis and better survival rate
• aberrant cell cycle pattern characterized by decreased quiescent (G0) or increased cycling (S/G2M) cells in common myeloid progenitors (CMPs), megakaryocyte-erythrocyte progenitors (MEPs), and bone marrow hematopoietic stem cell populations of mutants after 8 weeks of low-dosage mitomycin C treatment
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endocrine/exocrine glands
• 2 month old females show degenerated follicles
|
small ovary
(
J:224688
)
• in 2 month old mice
|
small testis
(
J:224688
)
• in 2 month old mice
|
hematopoietic system
pancytopenia
(
J:224688
)
• mice are susceptible to high-dose acute mitomycin C-exposure induced pancytopenia, with reduced bone marrow cellularity, hemoglobin, and platelet counts, and die within 15 days of treatment mostly due to bone marrow failure
• mice treated weekly with low dosage mitomycin C exhibit pancytopenia around 6-8 weeks, with reduction in number of white blood cells, red blood cells, platelet counts, and hemoglobin level, a decrease in the LK compartment, particularly megakaryocyte-erythrocyte progenitors, and a progressive reduction of phenotypic bone marrow hematopoietic stem cells
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• hematopoietic stem cells show a defect in long-term multilineage reconstitution for myeloid, B, and T cells in lethally irradiated recipient mice, although to a lesser extent than seen in homozygous Fancatm1.1Wong or
Fancctm1Mab mice
• mice treated with mitomycin C show a greater reduction of basophilic erythroblasts and late basophilic and chromatophilic erythroblasts but not orthochromatophilic erythroblasts compared to wild-type mice, an increase in more mature reticulocyte population, and a greater decrease in common myeloid progenitors in the LK population and in common lymphoid progenitors
• however, mice show normal hematological parameters in the peripheral blood, bone marrow cellularity, and lineage differentiation at steady state
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