| Budget Amount *help |
¥20,020,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥4,620,000)
Fiscal Year 2013: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2012: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2011: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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| Research Abstract |
We originally identified a metalloendopeptidase nardylisin (NRDc) as a binding partner of HB-EGF and reported that NRDc enhances ectodomain shedding of multiple membrane proteins. We generated NRDc-deficient (Nrd1-/-) mice and demonstrated that NRDc critically regulates axonal maturation and myelination in the central and peripheral nervous system through the regulation of neuregulin-1 shedding.
Here, we demonstrate that Nrd1-/- mice show severe hypotension and bradycardia. In spite of these phenotypes, analysis of heart rate variability and serum catecholamine levels revealed that sympathetic activity is upregulated in Nrd1-/- mice. Furthermore, Nrd1-/- mice showed abnormal sympathetic innervation patterning. Pharmacological blocking of autonomic nervous system showed that the intrinsic heart rate of Nrd1-/- mice was significantly decreased. In conclusion, NRDc critically regulates circulatory dynamics through modulating intrinsic heart rate and cardiac sympathetic innervation.
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