An attempt to identify the Darier's disease gene and to clarify its function

从1994年起，我们的目标一直集中在达里尔氏病（DD）基因的识别上。不幸的是，至少对我们来说， DD基因被英国小组发现为丝氨酸/内聚视网膜Ca ATP酶2型异构体（基因符号：ATP 2A 2）， 1999年3月。在此基础上，我们搜寻了一种色素细胞中的钙ATP酶，其中用于Hailey-Hailey疾病的基因（HHD），其中将其与DD的临床和历史特征部分分享。最近，我们发现了ATP 2C 1中的突变，一个Yast Golgi Ca ATPase和HHD的人类同源物。关于其他方面，我们研究了由最近创新的高度可靠的定量RT-PCR系统中ATP 2A 2 mRNA表达的特定位点，并通过紫外线诱导了ATP 2A 2的调制。根据结果，ATP 2A 2在正常人皮肤区域的表达水平，DD中的预测站点比那些在非西伯利亚区域的低。我们进一步观察到，文化正常角蛋白中基因的表达在超紫外线B辐射（30 mJ/cm Y D12 Y D1）后被抑制了1和3小时，并在辐射后至少12小时恢复了。These Observations Sugggest that seborrheic area，特定的低水平表达的ATP 2A 2可能帐户for the unique distribution of skin eruptions seen in the patients， and that suppression of the gene expression by environmental factor such as ultraviolet B可能involve in the formation of the skin lesions in vivo。

From 1994, our purpose has been focused on the identification of the Darier's disease (DD) gene. Unfortunately, at least for us, DD gene was found to be sarco/endoplasmic reticulum Ca ATPase type 2 isoform (gene symbol: ATP2A2) by British group in March, 1999. Subsequently, we searched for a Ca ATPase in a chromosomal lesion which harbors the gene for Hailey-Hailey disease (HHD) which shares in part the clinical and histological features with DD. And very recently, we have found that mutations in ATP2C1, a human homolog of a yeast Golgi Ca ATPase, cause HHD.On the other hand, we examined the site specific, and UV induced modulation of mRNA expression of ATP2A2 in human keratinocytes by recently-innovated highly reliable quantitative RT-PCR system. As the results, the expression levels of ATP2A2 in seborrheic areas of normal human skin, the predilected sites in DD, were lower than those in non-seborrheic areas. We further observed that the expression of the gene in cultured normal keratinocytes was suppressed 1 and 3 hr after ultraviolet B irradiation (30mJ/cmィイD12ィエD1), and recoverd at least 12 hr after irradiation. These observations suggest that seborrheic area, specific low level expressions of ATP2A2 may account for the unique distribution of skin eruptions seen in the patients, and that suppression of the gene expression by environmental factors such as ultraviolet B may involve in the formation of the skin lesions in vivo.