Mikoshiba K, Okano H, Aruga J, Tamura T, Miura M, Ikenaka K, Nakagawa T
Institute for Protein Research, Osaka University, Japan.
Ann N Y Acad Sci. 1990;605:166-82. doi: 10.1111/j.1749-6632.1990.tb42391.x.
The shiverer and myelin-deficient (mld) mutants are two allelic mutations. Both are characterized by hypomyelination in the CNS and deficient expression of the MBP gene. Chimeric analysis of the pathogenesis of shiverer showed that shiverer mutation acts intrinsic to the oligodendrocyte, which is the only cell type expressing the MBP gene in the CNS. Molecular genetic studies by several groups demonstrated that shiverer is a deletion mutation in the MBP gene. Consequently, no MBP is produced in the shiverer mutant. In mld, however, partial expression of the MBP gene was observed. Interestingly, MBP was expressed in a mosaic fashion in the CNS of mld mice. Molecular genetic studies revealed that the mld mutant has duplicated MBP genes in tandem on a distal part (E2-4) of chromosome 18q. The reduced expression was based on the level of mRNA. A large portion is inverted in the upstream copy, and an intact copy is located downstream. We showed in mld mutants that antisense RNA corresponding to the inverted segment is transcribed, and it forms RNA duplex, with the RNA transcribed from the normal gene located downstream.
颤抖鼠和髓磷脂缺乏（mld）突变体是两个等位基因突变。两者的特征均为中枢神经系统髓鞘形成不足以及髓磷脂碱性蛋白（MBP）基因表达缺陷。对颤抖鼠发病机制的嵌合体分析表明，颤抖鼠突变在少突胶质细胞内起作用，少突胶质细胞是中枢神经系统中唯一表达MBP基因的细胞类型。多个研究小组的分子遗传学研究表明，颤抖鼠是MBP基因的缺失突变。因此，在颤抖鼠突变体中不产生MBP。然而，在mld中，观察到MBP基因有部分表达。有趣的是，MBP在mld小鼠的中枢神经系统中呈镶嵌式表达。分子遗传学研究表明，mld突变体在18号染色体长臂远端部分（E2 - 4）有串联重复的MBP基因。表达降低是基于mRNA水平。上游拷贝中有很大一部分是反向的，完整拷贝位于下游。我们在mld突变体中发现，与反向片段对应的反义RNA被转录，并与下游正常基因转录的RNA形成RNA双链体。
