beta-galactosidase-deficient mouse as an animal model for G(M1)-gangliosidosis
beta-galactosidase-deficient mouse as an animal model for G(M1)-gangliosidosis
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DOI：
10.1023/a:1018573518127
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发表时间：
1997-09-01
影响因子：
3
通讯作者：
Naiki, M
中科院分区：
文献类型：
--
作者：
Matsuda, J;Suzuki, O;Naiki, M
G（M1）-神经节苷脂病是一种由溶酶体酸性β-半乳糖苷酶缺乏引起的人类进行性神经系统疾病，该酶水解神经节苷脂G（M1）和其他糖缀合物的末端β-半乳糖苷残基。在这项研究中，我们建立了一个小鼠模型G（M1）-神经节苷脂沉积症的基因靶向胚胎干细胞。β-半乳糖苷酶基因被破坏的纯合子小鼠表现出β-半乳糖苷酶缺乏，表现为进行性痉挛性双瘫，并在7-10月龄时死于消瘦。病理学上，PAS阳性胞浆内的存储中观察到的神经元细胞在大脑中的各个领域。生化分析显示，神经节苷脂G（M1）和去唾液酸G（M1）在脑组织中的显着积累。该动物模型的建立将为人类G（M1）-神经节苷脂病的发病机制分析和治疗试验提供重要的实验依据。
G(M1)-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 G(M1) and other glycoconjugates. In this study, we generated a mouse model for G(M1)-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 G(M1) and asialo G(M1) in brain tissue. This animal model will be useful for pathogenetic analysis and therapeutic trial of human G(M1)-gangliosidosis.