A functional role for complex gangliosides: Motor deficits in GM2/GD2 synthase knockout mice
A functional role for complex gangliosides: Motor deficits in GM2/GD2 synthase knockout mice
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DOI：
10.1006/exnr.2000.7504
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发表时间：
2000-12-01
影响因子：
5.3
通讯作者：
Schnaar, RL
中科院分区：
文献类型：
--
作者：
Chiavegatto, S;Sun, J;Schnaar, RL
虽然神经节苷脂是所有脊椎动物神经细胞上丰富的分子决定簇（约占脑干重的1.5%），但其功能仍不清楚。我们报告说，小鼠工程缺乏复杂的神经节苷脂生物合成的关键酶（GM 2/GD 2合酶），并只表达简单的神经节苷脂分子种类GM 3和GD 3，发展显着和进行性行为神经病变，包括反射，力量，协调和平衡的缺陷。在8和12个月大时应用的运动能力的定量指数也显示与对照组相比，复杂神经节苷脂敲除小鼠中的进行性步态障碍，包括步幅长度减少、步幅宽度减少和后爪印长度增加以及直立显著减少。与对照组相比，无效突变小鼠倾向于以小的费力运动行走。10个月大的复杂神经节苷脂敲除小鼠也显示出震颤和僵住症的显著发生率。这些全面的神经行为研究确立了复合神经节苷脂在维持小鼠正常神经生理学中的重要作用，与维持轴突和髓磷脂中的作用一致（Sheikh，K. A.、J.孙，Y. Liu，H.卡瓦伊T. O.克劳福德河，巴西-地L. Proia，J. W. Griffin和R. L. Schnaar. 1999.缺乏复合神经节苷脂的小鼠会发生沃勒变性和髓鞘形成缺陷。Proc. Natl. Acad. Sci. USA 96：7532-7537），并且可以提供对某些神经退行性疾病的潜在机制的见解，（C）2000 Academic Press。
Although gangliosides are abundant molecular determinants on all vertebrate nerve cells (comprising approximate to1.5% of brain dry weight) their functions have remained obscure. We report that mice engineered to lack a key enzyme in complex ganglioside biosynthesis (GM2/GD2 synthase), and which express only the simple ganglioside molecular species GM3 and GD3, develop significant and progressive behavioral neuropathies, including deficits in reflexes, strength, coordination, and balance. Quantitative indices of motor abilities, applied at 8 and 12 months of age, also revealed progressive gait disorders in complex ganglioside knockout mice compared to controls, including reduced stride length, stride width, and increased hindpaw print length as well as a marked reduction in rearing. Compared to controls, null mutant mice tended to walk in small labored movements. Twelve-month-old complex ganglioside knockout mice also displayed significant incidence of tremor and catalepsy. These comprehensive neurobehavioral studies establish an essential role for complex gangliosides in the maintenance of normal neural physiology in mice, consistent with a role in maintaining axons and myelin (Sheikh, K. A., J. Sun, Y. Liu, H. Kawai, T. O. Crawford, R. L. Proia, J. W. Griffin, and R. L. Schnaar. 1999. Mice lacking complex gangliosides develop Wallerian degeneration and myelination defects. Proc. Natl. Acad. Sci. USA 96: 7532-7537), and may provide insights into the mechanisms underlying certain neural degenerative diseases, (C) 2000 Academic Press.