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

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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.