Mechanisms for the biosignal regulation with glycosphingolipids and their redundancy

1.对GM2/GD2合酶和GD3合酶基因双敲除(KO)小鼠的分析表明，神经变性、皮肤损伤、抗焦虑、记忆和学习能力下降、感觉功能下降、乙酰胆碱M受体的反应性降低和5-HT2受体的敏感性增加，表明酸性神经节苷脂在神经组织的维持中是必不可少的。基因表达谱结果显示，D-KO小鼠中有5个基因减少，15个基因增加。特别是，补体因子及其受体被上调，表明筏子中补体调节分子的功能障碍和由此导致的组织损伤导致补体激活，导致病情恶化。舌下神经分化实验显示，GM2/GD2Synthase KO小鼠的再生活性降低，用激光共聚焦显微镜和RT-PCR法分析KO小鼠舌下神经核内下调的基因显示ExpR…更多的BDNF和GDNF等基因表达下调，提示GD3可能不足以补偿ASIALO系列结构失去的功能。β4GalT-VI基因KO小鼠的糖脂组成无明显变化，而β4GaIT-V.5似乎可进行乳胶合成。GM3合成酶基因KO小鼠出生和成长过程中未见明显异常，提示积雪草酸系列糖脂具有代偿作用。Gb3/CD77合酶基因KO小鼠对Vero毒素不敏感，表明它在对毒素的反应中起着唯一的作用。综上所述，通过观察哪些方面可以被剩余的糖脂补偿，哪些方面不能。在未来的计划中，以下主题似乎很重要。即1.基于单基因KO和D-KO小鼠表型的比较，分析特定糖脂的作用。2.特定糖脂特异性配基分子的鉴定。3.体内糖脂通过形成簇发挥作用的膜微区的分析。较少

1. Analyses of double knockout (KO) mice of GM2/GD2synthase and GD3 synthase genes revealed nerve degeneration, skin lesions, anti-anxiety, reduced memory and learning, reduced sensory function, lower responsiveness of acetylcholine muscarinic receptor and increased sensitivity of serotonin 5-HT2 receptor, suggesting that acidic glycosphingolipids are essential in the maintenance of nervous tissues.2. Gene expression profiling resulted in the identification of 5 genes reduced and 15 genes increased in the D-KO mice. In particular, complement factors and those receptors are up-regulated, indicating that dysfunction of complement-regulatory molecules in rafts and resulting tissue damages induced complement activation, leading to exacerbation of3. deggnnertiion experiments of hypoglossal nerves showed reduced regenerative activity in the GM2/GD2synthase KO mice, Analysis of genes which are down-regulated in the hypoglossal nerve nuclei in the KO mice with LCM and RT-PCR revealed that expr … More ession of BDNF and GDNF etc are down-regulated, suggesting that GD3 may not be enough to compensate the lost function of asialo-series structures.4. β4GalT-VI gene KO mice showed no changes in glycolipid composition, and lac-cer synthesis seemed to be performed with β4GaIT-V.5. GM3 synthase gene KO mice were born and grew up with no apparent abnormality, suggesting the compensation effects with asialo-series glycolipids.6. Gb3/CD77 synthase gene KO mice showed no sensitivity to verotoxins, suggesting its exclusive role in the response to the toxins.To summarize, it has become possible to see through which aspects can be compensated by the remaining glycolipids and which ones not. In the future plan, following themes seem to be important. i.e. 1. analysis of roles of particular glycolipids based on the comparison of phenotypes between single gene KO and D-KO mice. 2. Identification of ligand molecules specific for particular glycolipid. 3. analysis of membrane microdomains in vivo where glycolipids play roles by forming clusters. Less