| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Research Abstract |
Approximately 50% of aged SMAP1(-/-) mice developed anemia associated with morphologically dysplastic cells of erythroid-myeloid lineage, which are hematological abnormalities reminiscent of those seen in myelodysplastic syndrome (MDS) in humans. Furthermore, some SMAP1(-/-) mice developed acute myeloid leukemia (AML) of various subtypes. The transport analysis showed that transferrin endocytosis was enhanced in erythroblasts of SMAP1(-/-) mice. In mast cells cultured in stem cell factor, SMAP1 deficiency did not affect the internalization of c-Kit but impaired the sorting of internalized c-Kit from multivesicular bodies to lysosomes, which caused the intracellular accumulation of undegraded c-Kit accompanied by a significant increase in ERK phosphorylation and cell growth activity. Collectively, these results provide the first evidence in a mouse model that the deregulation of clathrin-dependent membrane trafficking involving the transferrin receptor and c-Kit may be involved inthe development of MDS and subsequent AML.
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