Gene expression and its application to the investigation on pathogenesis of congenital metabolic diseases and development of therapy for them.

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Effors were directed to clarify the pathogenesis of Fabry disease and galactosialidosis and develop the therapy for these diseases by means of gene expression system.Fabry disease is an X-linked inborn error of glycosphingolipid catabolism resulting from the deficient activity of alpha-galactosidase. The specific alpha-galactosidase mutations that cause the classic or variant Fabry disease phenotypes have been deterined. A variety of mutations, including deletions, nonsense mutations, splicing mutations and amino acid substitutions caused complete deficiency of alpha-galactosidase activity and resulted in the classic form of Fabry manifestations. Single base substitutions between 5'-end and the center of exon 6 led to the residual enzyme activity and variant form of Fabry phenotype. A large amount of human alpha-galactosidase was expressed using recombinant baculovirus/insect cell expression system and a possibility of enzyme replacement therapy for Fabry disease was investigated.A genetic defect of protective protein causes an systemic disease, galactosialidosis. Expression of human protective protein was established in transformed Chinese hamster ovary cells, and purified protective protein was confirmed to be a multifunctional enzyme protein.