Kimura M, Sato M, Akatsuka A, Saito S, Ando K, Yokoyama M, Katsuki M
Division of Molecular Life Science, School of Medicine, Tokai University, Bohseidai, Isehara, Kanagawa 259-11, Japan.
Brain Res. 1998 Mar 2;785(2):245-52. doi: 10.1016/s0006-8993(97)01383-8.
Shiverer (shi) mice, which are neurologically mutant, lack a large portion of the gene for the myelin basic proteins (MBPs), have virtually no myelin in their central nervous system (CNS), and shiver, undergo seizures, and die early. At least five types of MBPs (21.5, 18.5, 17.3, 17.2 and 14.0 kDa) are known to be generated through alternative splicing from a single MBP gene. We have produced transgenic shi mice carrying a cDNA encoding mouse 14-kDa MBP isoform, the most abundant form of MBPs, under control of a mouse MBP gene promoter, and showed that expression of the 14-kDa MBP can restore CNS myelination. To test whether the 17.2-kDa MBP isoform, one of the minor components of MBPs, can also elicit myelination in homozygous shi mutants, we produced seven independent transgenic shi mice carrying cDNA encoding the mouse 17.2-kDa MBP isoform, and the transcription of which was driven by a mouse MBP gene promoter. The axons in the cerebellum of one transgenic line, which exhibited the highest expression of transgene-derived mRNA ( approximately 50% of the level of total MBP mRNA in the normal mouse brain), were myelinated. This mouse exhibited nearly normal behavior. These findings indicate that the 17.2-kDa MBP isoform, even when the only 17.2-kDa MBP isoform is present, has the ability to elicit CNS myelination in transgenic shi mice. This transgenic strategy will be useful for elucidating the role of each type of MBP isoform in CNS myelinogenesis.
颤抖（shi）小鼠是神经学上的突变体，缺乏髓鞘碱性蛋白（MBP）基因的很大一部分，其中枢神经系统（CNS）几乎没有髓鞘，会颤抖、癫痫发作并早亡。已知至少有五种类型的MBP（21.5、18.5、17.3、17.2和14.0 kDa）是通过单个MBP基因的可变剪接产生的。我们制备了转基因shi小鼠，其携带在小鼠MBP基因启动子控制下编码小鼠14 kDa MBP异构体（MBP最丰富的形式）的cDNA，并表明14 kDa MBP的表达可以恢复CNS髓鞘形成。为了测试MBP的次要成分之一17.2 kDa MBP异构体是否也能在纯合shi突变体中引发髓鞘形成，我们制备了七只独立的转基因shi小鼠，它们携带编码小鼠17.2 kDa MBP异构体的cDNA，其转录由小鼠MBP基因启动子驱动。一个转基因系的小脑中的轴突有髓鞘形成，该系表现出转基因衍生mRNA的最高表达（约为正常小鼠脑中总MBP mRNA水平的50%）。这只小鼠表现出近乎正常的行为。这些发现表明，即使仅存在17.2 kDa MBP异构体，17.2 kDa MBP异构体也有能力在转基因shi小鼠中引发CNS髓鞘形成。这种转基因策略将有助于阐明每种类型的MBP异构体在CNS髓鞘形成中的作用。
