Matsuda J, Suzuki O, Oshima A, Ogura A, Noguchi Y, Yamamoto Y, Asano T, Takimoto K, Sukegawa K, Suzuki Y, Naiki M
Department of Veterinary Science, National Institute of Health, Tokyo, Japan.
Glycoconj J. 1997 Sep;14(6):729-36. doi: 10.1023/a:1018573518127.
GM1-gangliosidosis is a progressive neurological disease in humans caused by deficiency of lysosomal acid beta-galactosidase, which hydrolyses the terminal beta-galactosidic residue from ganglioside GM1 and other glycoconjugates. In this study, we generated a mouse model for GM1-gangliosidosis by gene targeting in embryonic stem cells. The mouse homozygous for the disrupted beta-galactosidase gene showed beta-galactosidase deficiency, presented with progressive spastic diplegia, and died of emaciation at 7-10 months of age. Pathologically, PAS-positive intracytoplasmic storage was observed in neuronal cells of various areas in the brain. Biochemical analysis revealed a marked accumulation of ganglioside GM1 and asialo GM1 in brain tissue. This animal model will be useful for pathogenetic analysis and therapeutic trial of human GM1-gangliosidosis.
GM1神经节苷脂贮积症是一种人类进行性神经疾病，由溶酶体酸性β-半乳糖苷酶缺乏引起，该酶可水解神经节苷脂GM1和其他糖缀合物末端的β-半乳糖苷残基。在本研究中，我们通过对胚胎干细胞进行基因靶向操作，构建了GM1神经节苷脂贮积症的小鼠模型。β-半乳糖苷酶基因破坏的纯合小鼠表现出β-半乳糖苷酶缺乏，出现进行性痉挛性双瘫，并在7至10月龄时死于消瘦。病理上，在脑内不同区域的神经元细胞中观察到PAS阳性胞浆内蓄积。生化分析显示脑组织中神经节苷脂GM1和脱唾液酸GM1明显蓄积。该动物模型将有助于人类GM1神经节苷脂贮积症的发病机制分析和治疗试验。
