| Project/Area Number |
18390250
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | The University of Tokushima |
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Principal Investigator |
MIYAMOTO Ken-ichi The University of Tokushima, Institute of health biosciences graduate school, Professor (70174208)
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| Co-Investigator(Kenkyū-buntansha) |
KUWAHATA Masashi The University of Tokushima, Institute of health biosciences graduate school, Lecturer (30304512)
SEGAWA Hiroko The University of Tokushima, Institute of health biosciences graduate school, Assistant professor (70325257)
TATSUMI Sawako The University of Tokushima, Institute of health biosciences graduate school, COE Fellow researchm (80420545)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,500,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥900,000)
Fiscal Year 2007: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2006: ¥12,600,000 (Direct Cost: ¥12,600,000)
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| Keywords | kidney / phosphate / HHRH / hypophosphatemia / mineralization / rickets |
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| Research Abstract |
Phosphate (Pi) has long been recognized to play an important role in bone mineralization.
The homeostatic maintenance of extracellular phosphate is achieved primarily by re-absorption of phosphate in the proximal kidney tubule through the hormone- and phosphate sensitive sensor protein (type II Na/Pi cotrnsporter. Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare inherited disorder in an autosomal recessive fashion, characterized by hypophosphatemia, short stature, rickets and/or osteomalacia and secondary absorptive hypercalciuria. More recently, linkage analysis of HHRH demonstrated that the candidate gene is the phosphate sensor (type IIc Na/Pi (NaPi-IIc) cotransporter). In the present study, we demonstrated that lack of functional NaPi-IIc protein with HHRH results in severe renal Pi-wasting, leading to hypophosphatemia (10). These observations suggest that the NaPi-IIc cotransporter has an important role in renal Pi reabsorption and bone mineralization, and may be a key determinant of plasma Pi concentrations in human (11). However, it is not clear why loss of function of the less abundant and energetically less favorable electroneutral NaPi-Iic transporter causes rickets and osteomalacia in humans whereas mutations in the more abundant electrogenic NaPi-Iia transporter elicits a mild skeletal phenotype that lacks the typical features of rickets and osteomalacia in mice. To understand the role of NaPi-Iia and NaPi-Iic transporters in the overall maintenance of Pi homeostasis and bone mineralization, we have disrupted the murine NaPi-Iia/NaPi-Iic gene and analyzed phenotypes of each mutant. The present studies suggest that NaPi-Iic may be a more important regulator of Pi homeostasis in humans than in mice.
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