MOLECULAR BASIS OF CEREBRAL DEGENERATION

三种人类溶酶体基因：β-半乳糖苷酶、氨基己糖苷酶 A 和 氨基己糖苷酶 B 将被克隆。 每个的 cDNA 将从 通过筛选抗体反应性人肝 lambda gtll 文库 牌匾。 全长 cDNA 将被分离并测序以确定 与每种蛋白质的氨基酸序列的共线性。 与的比较 mRNA分析后将产生具有GM1和GM2神经节苷脂沉积症的突变体 和基因组片段以确定选定的核酸缺陷 细胞系。 β-半乳糖苷酶 cDNA 将被插入到表达中 将尝试对带有 GM1 的比格犬进行载体和基因治疗 神经节苷脂沉积症。

Three human lysosomal genes, beta-galactosidase, hexosaminidase A and hexosaminidase B, will be cloned. cDNA's for each will be isolated from a human liver lambda gtll library by screening for antibody reactive plaques. Full-length cDNA's will be isolated and sequenced to establish colinearity with amino acid sequences for each protein. Comparisons with mutants with GM1 and GM2 gangliosidosis will be made after analysis of mRNA and genomic fragments to establish the nucleic acid defects in selected cell lines. Beta-galactosidase cDNA will be inserted into an expression vector and gene therapy will be attempted in beagles with GM1 gangliosidosis.