|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1994 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1993 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Chronic granulomatous disease (CGD) is a rare inherited disorder where phagocytes can not generate superoxide anion and is characterized by recurrent, life-threatening infections with catalase positive-micro Organisms. The superoxide generating system in phagocytes consists of a membrane-bound catalytic component, cytochrome b558, (gp91-phox and p22-phox, ) and cytosolic components (p47-phox and p67-phox and rac p21). A functionally active enzyme complex is formed upon stimulation by assembly of the components on the plasma membrane.
In this project, we identified molecular defects of six CGD patients with p47-phox deficiency (BBRC 199 : 1372-1377,1994) and one with p67-phox deficiency (Blood in press). In the result of a statistical analysis of CGD patients in Japan, the incidence of this disease was no less than 4 out of one million births. We also analyzed the translocation mechanisms of racp21 protein to membrane (BBRC 195 : 264-269,1993) and that of p47-phox to p22-phox with the interaction between src homology locus (SH3) of the farmer and the proline rich region of the latter (PNAS 91 : 5345-5349,1994). We also found the region adjacent to His-94 in p22-phox is involved in the superoxide production in a cell free system that was shown by the inhibition with synthetic peptides corresponding the region (BBRC 204 : 924-929,1994).