1 Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
ASN Neuro. 2017 Jul-Aug;9(4):1759091417720583. doi: 10.1177/1759091417720583.
Alterations in the myelin proteolipid protein gene ( PLP1) may result in rare X-linked disorders in humans such as Pelizaeus-Merzbacher disease and spastic paraplegia type 2. PLP1 expression must be tightly regulated since null mutations, as well as elevated PLP1 copy number, both lead to disease. Previous studies with Plp1-lacZ transgenic mice have demonstrated that mouse Plp1 ( mPlp1) intron 1 DNA (which accounts for slightly more than half of the gene) is required for the mPlp1 promoter to drive significant levels of reporter gene expression in brain. However not much is known about the mechanisms that control expression of the human PLP1 gene ( hPLP1). Therefore this review will focus on sequences in hPLP1 intron 1 DNA deemed important for hPLP1 gene activity as well as a couple of "human-specific" supplementary exons within the first intron which are utilized to generate novel splice variants, and the potential role that these sequences may play in PLP1-linked disorders.
髓鞘碱性蛋白脂蛋白基因（PLP1）的改变可能导致人类罕见的 X 连锁疾病，如 Pelizaeus-Merzbacher 病和痉挛性截瘫 2 型。PLP1 的表达必须受到严格调控，因为缺失突变以及 PLP1 拷贝数的增加都会导致疾病。以前使用 Plp1-lacZ 转基因小鼠的研究表明，小鼠 Plp1（mPlp1）内含子 1 DNA（占基因的略多于一半）对于 mPlp1 启动子驱动脑内报告基因表达的显著水平是必需的。然而，对于控制人类 PLP1 基因（hPLP1）表达的机制知之甚少。因此，本综述将重点介绍 hPLP1 内含子 1 DNA 中被认为对 hPLP1 基因活性重要的序列，以及第一个内含子内的几个“人类特异性”补充外显子，这些外显子用于产生新的剪接变体，以及这些序列可能在 PLP1 相关疾病中发挥的作用。
