| Budget Amount *help |
¥33,800,000 (Direct Cost: ¥26,000,000、Indirect Cost: ¥7,800,000)
Fiscal Year 2010: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Fiscal Year 2009: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Fiscal Year 2008: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
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| Research Abstract |
Nardilysin (N-arginine dibasic convertase ; NRDc) is a metalloendopeptidase of M16 family. We have generated NRDc knockout mice (NRDc-/-) by gene targeting. NRDc-/- mice showed cold-intolerance when exposed to cold temperature (4℃). Brown adipose tissue (BAT) is specialized for adaptive thermogenesis in response to cold exposure, which occurs through the activity of uncoupling protein 1 (UCP1). UCP1, a mitochondrial inner-membrane protein, uncouples the mitochondrial proton gradient from ATP production, which results in heat generation. We have evaluated the expression of thermogenic genes including UCP1 in BAT of wild-type (NRDc+/+) and NRDc-/- mice. Quantitative RT-PCR (qRT-PCR) analysis revealed that UCP1 mRNA expression level of NRDc-/- BAT did not change after cold exposure, while that of NRDc+/+ BAT was markedly increased. We have also evaluated changes in tail blood flow after cold exposure by using laser doppler flowmetry. While tail blood flow of NRDc+/+ mice was dramatically reduced after cold exposure, that of NRDc-/- mice was not affected. These results indicate that NRDc-/- mice could not keep their body temperature after cold exposure because of (i) impaired adaptive thermogenesis and (ii) impaired vasoconstriction.
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