| Budget Amount *help |
¥28,730,000 (Direct Cost: ¥22,100,000、Indirect Cost: ¥6,630,000)
Fiscal Year 2011: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Fiscal Year 2010: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Fiscal Year 2009: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
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| Research Abstract |
Sphingosine 1-phosphate (S1P) is one of the most important lipid mediators and essential for cell migration. To elucidate a physiological role of SPNS2 in mammals, we analyzed Spns2-defecient mice. Spns2 transcripts were detected in vascular endothelial cells and S1P secretion were abolished in the vascular endothelial cells prepared from SPNS2-defecient mice. Consequently, blood plasma S1P concentration of SPNS2-defecient mice was reduced to approximately 60% of wild-type. Although about a half of S1P remaining in blood plasma, the blood of SPNS2-deficient mice contained significantly fewer lymphocytes. However, lymphocytes in SPNS2-defecient mice thymus express more S1p1 and show a high migration activity at a lower S1P concentration. These results suggested that S1P at microenvironments around the thymus endothelial cells is rather important for the lymphocytes egress from the thymus than overall S1P concentration in plasma.
Among the constructed various ABC transporters knockout mice, ABCA5 deficinet macrophage decrease cholesterol efflux and enhance the atheroscrelosis. These results suggested various orphan transporters play physiological important lipids odulators.
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