| Budget Amount *help |
¥11,300,000 (Direct Cost: ¥11,300,000)
Fiscal Year 2001: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1999: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Research Abstract |
The hypophosphatemic (Hyp) mouse is a murine homolog of human X-linked hypophosphatemia (XLH), the most frequently occurring form of heritable vitamin D-resistant rickets in humans, and has been used as an animal model for human XLH rickets. The cause of disorders related to XLH is considered to be primarily hypophosphatemia resulting from impaired renal phosphate reabsorption arising from a defect in phosphate transport at the brush border membrane. The purpose of the present study was to analyze whether several disorders other than hypophosphatemia cause local dentinal defects in Hyp mice. First, we compared serum phosphate levels and dentinal features of C57BL/6J Hyp/Y (Hyp) mice with C57BL/6J +/Y (Nor) mice obtained by breeding C57BL/6J Hyp/+ females with C57BL/6J Hyp/Y males. Wild type C57BL/6J +/Y (WT) mice were used as control animals. Widened predentin, which is one of the features of Hyp mice, was not observed in the teeth of Nor mice, although, statistically, serum phosphate levels in the Nor mice were lower than in the WT mice. In contrast, Hyp mice showed both widened predentin and decreased serum phosphate levels. Our results suggest that the hypomineralizatior of dentin seen in Hyp mice may not be caused by hypophosphatemia alone.
Next, we analyzed discrepancies in the distribution and quantity of OC protein and OC mRNA in odontoblasts between Hyp and WT mice. Hyp mice showed the same distribution of OC in odontoblasts and dentin as WT mice, however OC-like immunoreactivity in Hyp mice was weaker than in WT mice. On the other hand, WT mice expressed significantly OC mRNA more strongly than Hyp mice, suggesting that this reduction may have a role in the hypomineralization seen in the dentin of Hyp mice.
Based on our findings, the hypomineralization of dentin in Hyp mice may not be caused by hypophosphatemia alone, but also by a defect in odontoblasts, such as the reduction of OC expression.
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