Mechanisms for the biosignal regulation with glycosphingolipids and their redundancy

1.对GM 2/GD 2合酶和GD 3合酶基因双敲除（KO）小鼠的分析显示，神经变性、皮肤病变、抗焦虑、记忆和学习能力下降、感觉功能下降、乙酰胆碱M受体反应性降低和5-HT 2受体敏感性增加，提示酸性鞘糖脂在神经组织的维持中是必不可少的.基因表达谱分析结果表明，在D-KO小鼠中鉴定出5个基因减少，15个基因增加。特别是补体因子和那些受体被上调，表明筏中补体调节分子的功能障碍和由此产生的组织损伤诱导补体激活，导致3的恶化。GM 2/GD 2合酶基因敲除小鼠舌下神经核团的再生活性降低，LCM和RT-PCR分析舌下神经核团中表达下调的基因，结果表明，GM 2/GD 2合酶基因敲除小鼠舌下神经核团中表达下调的基因，在GM 2/GD 2合酶基因敲除小鼠舌下神经核团中表达下调的基因，在GM 2/GD 2合酶基因敲除小鼠舌下神经核团中表达下调的基因。 ...更多信息 BDNF、GDNF等的表达下调，提示GD 3可能不足以补偿去唾液酸序列结构的功能丧失.β4GalT-VI基因敲除小鼠的糖脂组成没有变化，乳糖合成似乎与β 4GalT-V有关。GM 3合酶基因敲除小鼠出生和生长发育无明显异常，提示去唾液酸系列糖脂具有代偿作用. Gb 3/CD 77合酶基因敲除小鼠对verotoxins不敏感，这表明它在对毒素的反应中起着独特的作用。总之，可以看出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小鼠之间表型的比较，分析特定糖脂的作用。2.特定糖脂特异性配体分子的鉴定。3.分析体内的膜微区，其中糖脂通过形成簇起作用。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