Zeller N K, Dubois-Dalcq M, Lazzarini R A
Laboratory of Molecular Genetics, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
J Mol Neurosci. 1989;1(3):139-49. doi: 10.1007/BF02918900.
The myelin-deficient (MD) rat does not express the major protein of CNS myelin, proteolipid protein (PLP). Here we further analyze whether this defect is reflected at the level of mRNA and whether the expression of other myelin proteins is affected in oligodendrocytes in vivo and in vitro. Both myelin basic protein (MBP) and PLP message levels were reduced in MD rats to 10-20% of the normal littermate controls, while the level of expression of an astrocyte-specific gene, glial fibrillary acidic protein (GFAP), was normal. Although MBP and PLP mRNAs were equally depressed, only MBP was detected with immunolabeling of corpus callosum, while PLP was absent in oligodendrocytes both in vivo and in vitro. A reduced number of MD rat oligodendrocytes express MBP in vitro compared to controls. The MD rat optic nerve contains normal numbers of 0-2A progenitors, but they tend to differentiate into GC-positive oligodendrocytes faster than oligodendrocytes from control littermates. In conclusion, the absence of PLP and reduced levels of MBP in the MD rats point to similarities with the jimpy mouse lesion. Moreover, the defect influences the expression of other myelin proteins and the oligodendrocyte developmental pathway.
髓磷脂缺陷(MD)大鼠不表达中枢神经系统髓磷脂的主要蛋白质——蛋白脂蛋白(PLP)。在此,我们进一步分析这种缺陷是否在mRNA水平上有所体现,以及在体内和体外的少突胶质细胞中,其他髓磷脂蛋白的表达是否受到影响。MD大鼠的髓磷脂碱性蛋白(MBP)和PLP的信使核糖核酸水平均降至正常同窝对照大鼠的10% - 20%,而星形胶质细胞特异性基因——胶质纤维酸性蛋白(GFAP)的表达水平则正常。尽管MBP和PLP的信使核糖核酸同样受到抑制,但通过胼胝体免疫标记仅检测到MBP,而在体内和体外的少突胶质细胞中均未检测到PLP。与对照相比,体外培养的MD大鼠少突胶质细胞中表达MBP的数量减少。MD大鼠视神经中0-2A祖细胞数量正常,但它们比对照同窝大鼠的少突胶质细胞更容易分化为GC阳性少突胶质细胞。总之,MD大鼠中PLP的缺失和MBP水平的降低表明其与jimpy小鼠病变存在相似之处。此外,这种缺陷影响了其他髓磷脂蛋白的表达以及少突胶质细胞的发育途径。