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

旨在阐明法布里病和半乳糖唾液中毒的发病机制，并利用基因表达系统开发治疗这些疾病的方法。法布里病是一种由α -半乳糖苷酶活性不足引起的糖鞘脂分解代谢的x连锁先天性错误。导致经典或变异法布里病表型的特定α -半乳糖苷酶突变已经确定。各种突变，包括缺失、无义突变、剪接突变和氨基酸替换，导致α -半乳糖苷酶活性完全缺乏，导致经典形式的法布里表现。外显子6 5′端和中心之间的单碱基替换导致酶活性的残留和法布里表型的变异形式。利用重组杆状病毒/昆虫细胞表达系统表达了大量人α -半乳糖苷酶，并探讨了酶替代治疗法布里病的可能性。保护蛋白的遗传缺陷导致全身性疾病——半乳糖唾液中毒。在转化的中国仓鼠卵巢细胞中建立了人保护蛋白的表达，纯化后的保护蛋白证实是一种多功能酶蛋白。

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.