| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
An animal model of hereditary 1,25-dihydroxyvitamin D-resistant rickets, generated by targeted ablation of the VDR in mice, results in hypocalcemia, hypophosphatemia, hyperparathyroidism, rickets, osteomalacia and alopecia. Normalization of mineral ion homeostasis by a diet high in calcium, phosphorus and lactose normalizes this phenotype with the exception of the alopecia. These results suggest that actions of the VDR (ligand-dependent or ligand-independent) are required for skin and hair follicle homeostasis.
Previously, we reported VDR knockout mice have a normal first hair coat but develop alopecia due to a defect in anagen initiation, and we identified the keratinocyte as the cell of origin of the defect. Furthermore, our results suggested that the abnormality is due to impaired ligand-independent receptor function. In spite of these abundant results, the target genes of vitamin D receptor in keratinocytes are unknown. Identification of target genes of VDR, concerning alopecia, might help us understanding the mechanism of maintenance of hair cycle and might give us a clue to prevent or cure alopecia accompanied with cancer chemotherapy or more general hair loss. Furthermore, our research might enable us to clarify the new mechanism and ligand-independent physiological functions of vitamin D receptor. To identify target genes of VDR, which is required for normal hair cycling, and to clarify ligand-independent physiological function of VDR, we performed some in vivo studies. 20days old VDR KO mice and control littermates were subjected to depilation to induce hair growth. 24hours after this procedure, RNA was isolated and subjected to cDNA array (once) and oligo array (twice) analysis and several factors were differentially expressed in all of these three experiments. We are now planning to perform in site hybridization to identify physiologically differentially expressed genes in vivo.
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