Turnley A M, Morahan G, Okano H, Bernard O, Mikoshiba K, Allison J, Bartlett P F, Miller J F
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Nature. 1991 Oct 10;353(6344):566-9. doi: 10.1038/353566a0.
Major histocompatibility complex (MHC) molecules are not normally expressed in the central nervous system (CNS). However, aberrant expression has been observed in multiple sclerosis lesions and could contribute to the destruction of myelin or the myelinating cells known as oligodendrocytes. The mechanism of cell damage associated with aberrant MHC molecule expression is unclear: for example, overexpression of class I and class II MHC molecules in pancreatic beta cells in transgenic mice leads to nonimmune destruction of the cells and insulin-dependent diabetes mellitus. We have generated transgenic mice that express class I H-2Kb MHC molecules, under the control of the myelin basic protein promoter, specifically in oligodendrocytes. Homozygous transgenic mice have a shivering phenotype, develop tonic seizures and die at 15-22 days. This phenotype, which we term 'wonky', is due to hypomyelination in the CNS, and not to involvement of the immune system. The primary defect appears to be a shortage of myelinating oligodendrocytes resulting from overexpression of the class I MHC molecules.
主要组织相容性复合体（MHC）分子通常不在中枢神经系统（CNS）中表达。然而，在多发性硬化症病变中已观察到异常表达，这可能导致髓鞘或称为少突胶质细胞的髓鞘形成细胞的破坏。与异常MHC分子表达相关的细胞损伤机制尚不清楚：例如，转基因小鼠胰腺β细胞中I类和II类MHC分子的过表达会导致细胞的非免疫性破坏以及胰岛素依赖型糖尿病。我们已培育出在髓鞘碱性蛋白启动子控制下，特别是在少突胶质细胞中表达I类H-2Kb MHC分子的转基因小鼠。纯合转基因小鼠具有颤抖的表型，会出现强直性惊厥，并在15至22天内死亡。我们将这种表型称为“摇摆”，它是由于中枢神经系统髓鞘形成不足所致，而非免疫系统的参与。主要缺陷似乎是由于I类MHC分子的过表达导致髓鞘形成少突胶质细胞短缺。
