Complex alternative splicing of the myelin oligodendrocyte glycoprotein gene is unique to human and non-human primates
Complex alternative splicing of the myelin oligodendrocyte glycoprotein gene is unique to human and non-human primates
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DOI：
10.1111/j.1471-4159.2006.04053.x
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发表时间：
2006-09-01
影响因子：
4.7
通讯作者：
Pham-Dinh, Danielle
中科院分区：
文献类型：
--
作者：
Delarasse, Cecile;Della Gaspera, Bruno;Pham-Dinh, Danielle
髓磷脂/少突胶质细胞糖蛋白 (MOG) 是中枢神经系统髓磷脂特异的次要整合膜蛋白，由位于主要组织相容性复合体中的基因编码。 MOG 是一种高度致脑炎的自身抗原，也是中枢神经系统炎症性脱髓鞘疾病中自身攻击性免疫反应的靶标。我们对仅在哺乳动物中枢神经系统中表达的基因——髓鞘少突胶质细胞糖蛋白（MOG）进行了转录组分析。与其他髓磷脂蛋白基因的模式不同，复杂的剪接模式只在灵长类动物中发现，而在小鼠中没有。除了啮齿动物共有的功能外，这些多种 MOG 亚型可能支持灵长类动物特有的功能，特别是维持髓磷脂结构、细胞内信号传导以及通过暴露特定 MOG 决定簇来调节 CNS 自身免疫。从发育角度来看，与其他髓磷脂蛋白不同，在人脑中，MOG 的剪接变体与主要亚型相比出现在较晚的阶段，与髓鞘形成和髓磷脂成熟同时发生。这些发现在近期哺乳动物进化中表型多样性的生物学基础框架内以及多发性硬化症等疾病的众所周知的可变临床表达的框架内进行了讨论。
Myelin/oligodendrocyte glycoprotein (MOG) is a minor integral membrane protein specific to CNS myelin, encoded by a gene located in the major histocompatibility complex. MOG is an highly encephalitogenic autoantigen and a target for autoaggressive immune responses in CNS inflammatory demyelinating diseases. We performed transcriptomic analyses for a gene expressed only in mammalian CNS, myelin oligodendrocyte glycoprotein (MOG). Complex splicing patterns were exclusively found in primates and not in mice, unlike patterns found for other myelin protein genes. In addition to those shared with rodents, these multiple MOG isoforms likely support functions unique to the primate order, in particular maintenance of myelin structure, intracellular signaling, and modulation of CNS autoimmunity via exposure of specific MOG determinants. Developmentally, in human brain the splice variants of MOG appear at a late stage compared to the major isoform, coincidental with myelination and myelin maturation, unlike other myelin proteins. These findings are discussed within the framework of a biological basis for phenotype diversity in recent mammalian evolution and for the notoriously variable clinical expression of diseases such as multiple sclerosis.