Research on Expression of Myelin-Associated Glycoprotein in Regeneration of Central Nervous System

髓鞘相关糖蛋白（MAG）是一种次要的髓鞘膜蛋白，作为免疫球蛋白超家族的一员，可能在细胞间相互作用中发挥作用。我们完成了小鼠MAG的cDNA克隆，发现了两种通过选择性剪接机制表达的MAG亚型（小MAG: S-MAG，大MAG: L-MAG）。为了阐明神经系统再生的机制之一，我们研究了MAG在神经系统损伤后髓鞘再生中的作用。本研究方案的结果如下：1)建立铜中毒小鼠脱髓鞘和再脱髓鞘实验模型。2)建立大脑中动脉闭塞致继发性脱髓鞘模型。3)利用合成的c端肽分别制备抗L-MAG和S-MAG抗体。4) Cuprison中毒诱导脱髓鞘后再脱髓鞘期L-MAG异构体。5)检测包括MAG在内的脑蛋白变化。6)在颤抖突变小鼠中，L-MAG在整个发育过程中几乎不表达。因此，L-MAG对正常髓鞘形成很重要。7)我们完成了人MAG的cDNA克隆，只获得了L-MAG的克隆。

The myelin-associated glycoprotein (MAG) is minor myelin membrans proteins and may play a role in cell to cell interaction as a member of immunoglobulin superfamily. We completed cDNA cloning of mouse MAG and found two kinds of MAG isoforms (small-MAG : S-MAG, large-MAG : L-MAG) which are expressed by alter native splicing mechanism. To clarify one of mechanisms of regeneration in nervous system, we examined roles of MAG on remyelination after damage of nervous system. The results of this research program are as follows.1) We established an experimental model of demyelination and remyelination by Cuprizon intoxication.2) An model of secondary demyelination by occlusion of middle cerebral artery was established.3) We prepared an anti-L-MAG and an anti-S-MAG antibodies from synthetic peptides of c-termini to L-MAG and S-MAG respectively.4) The L-MAG isoform was induced during remyelinating stage after demyelination by Cuprison intoxication.5) Changes of brain proteins including MAG were examined.6) In the quaking mutant mouse, L-MAG was scarcely expressed throughout development.Therefore, L-MAG is revealed to be important for normal myelination.7) We have completed cDNA cloning of human MAG and obtained only L-MAG clone.