|Budget Amount *help
¥6,700,000 (Direct Cost : ¥6,700,000)
Fiscal Year 1999 : ¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 1998 : ¥3,500,000 (Direct Cost : ¥3,500,000)
Transglutaminase 3 is an enzyme of which molecular weight is about 77 kDa. This enzyme is calcium-and thiol-dependent one and catalyze between lysine and glutamine residues of proteins. Therefore, iso-dipeptide crosslinks are made between cornified cell envelope protein precursors such as involucrin, small proline-rich proteins, elafin, cystatin A and loricrin. It is well known that transglutaminase 3 is distributed and granular layer of stratified epidermis. And this distribution pattern is almost same as loricrin.
Keratinizing disorders in skin are divided in 2 major groups. One is hereditary keratinizing disorders and another is non-hereditary keratinizing ones. Hereditary keratinizing disorders are hereditary ichthyoses, Darier disease, palmoplantar hyperkeratosis, porokeratosis and so on. However, diseases such as bullous congenital ichthyosiform erythroderma, annular epidermolytic ichthyosis, lamellar ichthyosis, some of palmoplantar karatodermas, pachyonychia congenita, Vohwinkel syndrome, some of progressive systemic erythrokeratoderma, Darier disease and Hailey-Hailey disease are now known to be caused by deletions and/or point mutations of specific genes. In contrast, the responsible genes for most of the hereditary keratinizing disorders are not known. I postulate the gene for transglutaminase 3 enzyme is one of the responsible genes for the hereditary keratinizing disorders. I try to make the knock out mouse of transglutaminase 3 gene. We screened the mouse transglutaminase 3 cDNA from mouse epidermis cDNA library. We are going to get a clone of genomic DNA from 129SV mouse genomic library next and finally make a targeting vector.