Woodruff R H, Franklin R J
MRC Cambridge Centre for Brain Repair and Department of Clinical Veterinary Medicine, University of Cambridge, UK.
J Neurocytol. 1998 Sep;27(9):683-93. doi: 10.1023/a:1006972316697.
During myelination, myelin proteins are expressed in a highly coordinated sequence. Of the four major isoforms of myelin basic protein, the proportion of the 21.5kDa and 17 kDa isoforms (which contain sequences encoded by myelin basic protein [MBP] exon 2) is enriched during active myelination in the mouse, suggesting that the alternative splicing of MBP transcripts containing exon 2 information is developmentally regulated. In this study, we compare the expression of MBP exon 1 and MBP exon 2 mRNAs in the neonatal rat spinal cord to establish whether developmental regulation of exon 2 mRNAs occurs in the rat in a manner similar to that previously described in the mouse. The expression of MBP mRNAs, together with that of proteolipid protein (PLP/DM-20) mRNA, in the developing white matter tracts increased dramatically between P7 and P10, corresponding to an increase in the extent of myelination. High levels of expression of each mRNA species examined were maintained between P10 and P14 as myelination proceeded. At P21, the expression of MBP exons 1 and 2 was reduced in the ventrolateral funiculi but was maintained at high levels in the dorsal funiculus. At P45, a further downregulation of both MBP mRNAs was apparent. By contrast, high levels of PLP/DM-20 expression were maintained from P10 onwards. In the grey matter, expression of MBP and PLP/DM-20 mRNAs increased more gradually and peak expression occurred later than in the white matter tracts. In this study, we therefore provide a description of myelin protein gene expression during post-natal development of the rat spinal cord. We have also shown that in the rat spinal cord, changes in the levels of MBP exon 2 expression associated with myelination reflect the changes of all MBP transcripts.
在髓鞘形成过程中,髓鞘蛋白按高度协调的顺序表达。在髓鞘碱性蛋白的四种主要亚型中,21.5kDa和17kDa亚型(包含由髓鞘碱性蛋白[MBP]外显子2编码的序列)的比例在小鼠活跃髓鞘形成期间增加,这表明包含外显子2信息的MBP转录本的可变剪接受到发育调控。在本研究中,我们比较新生大鼠脊髓中MBP外显子1和MBP外显子2 mRNA的表达,以确定外显子2 mRNA的发育调控在大鼠中是否以与先前在小鼠中描述的方式相似的方式发生。在发育中的白质束中,MBP mRNA以及蛋白脂蛋白(PLP/DM-20)mRNA的表达在P7和P10之间急剧增加,这与髓鞘形成程度的增加相对应。随着髓鞘形成的进行,在P10和P14之间,所检测的每种mRNA的高水平表达得以维持。在P21时,MBP外显子1和2在腹外侧索中的表达降低,但在背索中维持在高水平。在P45时,两种MBP mRNA的进一步下调明显。相比之下,从P10开始,PLP/DM-20的表达维持在高水平。在灰质中,MBP和PLP/DM-20 mRNA的表达增加更为缓慢,且峰值表达比白质束中出现得更晚。因此,在本研究中,我们描述了大鼠脊髓出生后发育过程中髓鞘蛋白基因的表达情况。我们还表明,在大鼠脊髓中,与髓鞘形成相关的MBP外显子2表达水平的变化反映了所有MBP转录本的变化。