identification of a factor affection hair cycle in VDR null mouse

一种遗传性1，25-二羟基维生素D抵抗软骨病的动物模型，通过靶向切除小鼠的VDR而产生，导致低钙血症、低磷血症、甲状旁腺功能亢进症、软骨病和脱发。通过高钙、高磷和高乳糖的饮食使矿物质离子平衡正常化，使这种表型正常化，脱发除外。这些结果表明，VDR(配体依赖或配体非依赖)的作用对于皮肤和毛囊的稳定是必需的。此前，我们报道了VDR基因敲除小鼠的第一层毛发正常，但由于生长期启动缺陷而患上脱发，我们确定角质形成细胞是该缺陷的起源细胞。此外，我们的结果表明，这种异常是由于配体非依赖性受体功能受损所致。尽管有这些丰富的结果，但角质形成细胞中维生素D受体的靶基因尚不清楚。发现VDR与脱发相关的靶基因，可能有助于我们了解头发周期的维持机制，并可能为预防或治疗伴随癌症化疗或更广泛的脱发的脱发提供线索。此外，我们的研究可能使我们能够阐明维生素D受体的新机制和非配体依赖的生理功能。为了确定正常毛发周期所需的VDR的靶基因，并阐明VDR的非配体依赖的生理功能，我们进行了一些体内研究。20日龄VDR KO小鼠和对照仔鼠进行脱毛诱导毛发生长。24小时后，提取RNA，进行基因芯片分析(一次)和寡核苷酸阵列分析(两次)，在这三个实验中都有几个因子的差异表达。我们现在正计划进行原位杂交，以确定体内生理差异表达的基因。

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.