Nadon N L, Duncan I D
Biology Department, University of Tulsa, Okla, USA.
Dev Neurosci. 1996;18(3):174-84. doi: 10.1159/000111406.
The shaking pup, a canine mutant, carries a point mutation in the myelin proteolipid protein (PLP) gene that causes dysmyelination of the central nervous system (CNS) with resultant tremor, seizures, and other persistent neurological deficits. The developmental potential of glial cells in the shaking pup CNS and peripheral nervous system (PNS) was evaluated by quantitative analysis of the expression of several glial-specific genes. All of the myelin-associated genes demonstrated developmental patterns of expression similar to those observed in the controls, but at significantly reduced levels. Expression of the genes for the major CNS myelin proteins, PLP and the myelin basic protein, are most dramatically affected in the shaking pup, although reduced expression levels are observed for other oligodendrocyte-specific genes such as 2',3'-cyclic nucleotide 3'phosphodiesterase and glucose phosphate dehydrogenase. The pattern of gene expression in the shaking pup indicates that the oligodendrocytes experience an inhibition in development after the myelination program has begun. There appears to be little evidence for an astrocytic response to the dysmyelinating condition at the RNA level, but we present evidence for ectopic expression of P0 mRNA in the CNS. Expression of the P0 and PLP genes in the sciatic nerve appears to be normal, reinforcing previous reports that PNS myelination is unaffected by the mutation in the PLP gene.
颤抖幼犬是一种犬类突变体，其髓磷脂蛋白脂蛋白（PLP）基因存在一个点突变，该突变导致中枢神经系统（CNS）髓鞘形成异常，进而引发震颤、癫痫发作以及其他持续性神经功能缺陷。通过对几种胶质细胞特异性基因表达的定量分析，评估了颤抖幼犬中枢神经系统和外周神经系统（PNS）中胶质细胞的发育潜能。所有与髓鞘相关的基因均呈现出与对照组相似的发育表达模式，但表达水平显著降低。在颤抖幼犬中，主要中枢神经系统髓鞘蛋白PLP和髓鞘碱性蛋白的基因表达受到的影响最为显著，不过其他少突胶质细胞特异性基因如2',3'-环核苷酸3'-磷酸二酯酶和葡萄糖磷酸脱氢酶的表达水平也有所降低。颤抖幼犬的基因表达模式表明，少突胶质细胞在髓鞘形成程序开始后其发育受到抑制。在RNA水平上，几乎没有证据表明星形胶质细胞对髓鞘形成异常状况有反应，但我们提供了中枢神经系统中P0 mRNA异位表达的证据。坐骨神经中P0和PLP基因的表达似乎正常，这进一步证实了先前关于外周神经系统髓鞘形成不受PLP基因突变影响的报道。
